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      Enhanced anti-mammary gland cancer activities of tamoxifen-loaded erythropoietin-coated drug delivery system

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          Abstract

          Nanomedicine is an emerging area in the medical field, particularly in the treatment of cancers. Nanostructured lipid carrier (NLC) was shown to be a good nanoparticulated carrier for the delivery of tamoxifen (TAM). In this study, the tamoxifen-loaded erythropoietin-coated nanostructured lipid carriers (EPO-TAMNLC) were developed to enhance the anti-cancer properties and targetability of TAM, using EPO as the homing ligand for EPO receptors (EpoRs) on breast cancer tissue cells. Tamoxifen-loaded NLC (TAMNLC) was used for comparison. The LA7 cells and LA7 cell-induced rat mammary gland tumor were used as models in the study. Immunocytochemistry staining showed that LA7 cells express estrogen receptors (ERs) and EpoRs. EPO-TAMNLC and TAMNLC significantly (p<0.05) inhibited proliferation of LA7 in dose- and time-dependent manner. EPO-TAMNLC induced apoptosis and G 0/G 1 cell cycle arrest of LA7 cells. Both drug delivery systems showed anti-mammary gland tumor properties. At an intravenous dose of 5 mg kg -1 body weight, EPO-TAMNLC and TAMNLC were not toxic to rats, suggesting that both are safe therapeutic compounds. In conclusion, EPO-TAMNLC is not only a unique drug delivery system because of the dual drug-loading feature, but also potentially highly specific in the targeting of breast cancer tissues positive for ERs and EpoRs. The incorporation of TAM into NLC with and without EPO coat had significantly (p<0.05) improved specificity and safety of the drug carriers in the treatment of mammary gland tumors.

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          Most cited references 32

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          A good practice guide to the administration of substances and removal of blood, including routes and volumes.

          This article is the result of an initiative between the European Federation of Pharmaceutical Industries Associations (EFPIA) and the European Centre for the Validation of Alternative Methods (ECVAM). Its objectives are to provide the researcher in the safety evaluation laboratory with an up-to-date, easy-to-use set of data sheets to aid in the study design process whilst at the same time affording maximum welfare considerations to the experimental animals. Although this article is targeted at researchers in the European Pharmaceutical Industry, it is considered that the principles underpinning the data sets and refinement proposals are equally applicable to all those who use these techniques on animals in their research, whether in research institutes, universities or other sectors of industry. The implications of this article may lead to discussion with regulators, such as those responsible for pharmacopoeial testing. There are numerous publications dealing with the administration of test substances and the removal of blood samples, and many laboratories also have their own "in-house" guidelines that have been developed by custom and practice over many years. Within European Union Directive 86/609EEC1 we have an obligation to refine experiments to cause the minimum amount of stress. We hope that this article will provide background data useful to those responsible for protocol design and review. This guide is based on peer-reviewed publications whenever possible, but where this is not possible we have used "in-house" data and the experience of those on the working party (as well as helpful comments submitted by the industry) for a final opinion. The guide also addresses the continuing need to refine the techniques associated with the administration of substances and the withdrawal of blood, and suggests ways of doing so. Data-sharing between laboratories should be encouraged to avoid duplication of animal work, as well as sharing practical skills concerning animal welfare and scientific problems caused by "overdosing" in some way or another. The recommendations in this guide refer to the "normal" animal, and special consideration is needed, for instance, during pregnancy and lactation. Interpretation of studies may be confounded when large volumes are administered or excessive sampling employed, particularly if anaesthetics are used. Copyright 2001 John Wiley & Sons, Ltd.
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            Mice anesthesia, analgesia, and care, Part I: anesthetic considerations in preclinical research.

            Animal experiments are necessary for a better understanding of diseases and for developing new therapeutic strategies. The mouse (Mus musculus) is currently the most popular laboratory animal in biomedical research. Experimental procedures on animals often require anesthesia and/or analgesia to obtain adequate immobilization and to reduce stress or pain. Mice anesthesia is challenging for several reasons including the animals' size, metabolic rate, and the high risk of hypothermia and hypoglycemia. Moreover, anesthetic agents influence physiological parameters, further interfering with experimental results. Small animal imaging procedures are increasingly used in biomedical research both because the animals allow in vivo monitoring and because they are readily available for longitudinal and noninvasive studies as well as investigations into the evolution of diseases and the effects of new therapies. Anesthesia must adapt to the imaging technique, the procedure length, and the aim of the study. The purpose of this article is to review the existing literature on anesthetic protocols adopted in mice for molecular imaging studies and to report our experience.
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              Normal structure, function, and histology of the bone marrow.

              While a complete blood count provides information regarding possible treatment-related effects reflected in the peripheral blood, morphological evaluation of bone marrow cytology and paraffin sections provides information about bone marrow tissue architecture that otherwise would be missed by examination of peripheral blood alone. In decalcified, paraffin-embedded, hematoxylin and eosin (H&E)-stained sections of bone marrow, the more mature stages of the erythroid and myeloid cells, adipocytes, mast cells, and megakaryocytes can be identified, but lymphoid cells as well as immature progenitor cells can not be reliably identified. The quality of the marrow sections is governed by numerous variables related to specimen collection and processing and must be considered. In addition to discussing normal structure, function, and histology of bone marrow, methods for preparation and evaluation of bone marrow are presented.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Project administrationRole: ResourcesRole: Supervision
                Role: ConceptualizationRole: MethodologyRole: Project administrationRole: ResourcesRole: Supervision
                Role: ConceptualizationRole: MethodologyRole: Project administrationRole: ResourcesRole: Supervision
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Resources
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Project administrationRole: Resources
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: ResourcesRole: Software
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                10 July 2019
                2019
                : 14
                : 7
                Affiliations
                [1 ] Institute of Bioscience, Universiti Putra Malaysia, UPM Serdang, Selangor, Malaysia
                [2 ] Faculty of Veterinary Medicine, Universiti Putra Malaysia, UPM Serdang, Selangor, Malaysia
                [3 ] Faculty of Medicine, Universiti Putra Malaysia, UPM Serdang, Selangor, Malaysia
                [4 ] Centre for Pre-University Studies, Faculty of Pharmacy, MAHSA University, Jenjarom, Kuala Langat, Selangor, Malaysia
                [5 ] School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia
                [6 ] School of Pharmacy, Faculty of Health and Medical Science, Taylor’s University, Subang Jaya, Selangor, Malaysia
                Columbia University, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Article
                PONE-D-18-32607
                10.1371/journal.pone.0219285
                6619690
                31291309
                © 2019 Beh et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Figures: 13, Tables: 3, Pages: 25
                Product
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100004530, Universiti Putra Malaysia;
                Award ID: GP-IPS/2017/9537700
                Award Recipient :
                Chaw Yee Beh has received the funding from Graduate Research Fellowship University Putra Malaysia with grant numbers GP-IPS/2017/9537700. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Biochemistry
                Lipids
                Biology and Life Sciences
                Anatomy
                Reproductive System
                Breast Tissue
                Mammary Glands
                Medicine and Health Sciences
                Anatomy
                Reproductive System
                Breast Tissue
                Mammary Glands
                Biology and Life Sciences
                Anatomy
                Exocrine Glands
                Mammary Glands
                Medicine and Health Sciences
                Anatomy
                Exocrine Glands
                Mammary Glands
                Medicine and Health Sciences
                Oncology
                Cancer Treatment
                Biology and Life Sciences
                Cell Biology
                Cell Processes
                Cell Death
                Apoptosis
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Breast Tumors
                Breast Cancer
                Biology and Life Sciences
                Toxicology
                Toxicity
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Toxicology
                Toxicity
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Medicine and Health Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Biology and Life Sciences
                Biochemistry
                Hormones
                Peptide Hormones
                Erythropoietin
                Custom metadata
                All relevant data are within the paper.

                Uncategorized

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