Thursday, 8 June 2017

Dactinomycin D dược chất kháng A549

A549 subclones demonstrate heterogeneity in toxicological sensitivity ...

Dactinomycin D

From Wikipedia, the free encyclopedia
Dactinomycin
Actinomycin D.png
Actinomycin D sticks.png
Clinical data
Trade namesCosmegen
AHFS/Drugs.comMonograph
MedlinePlusa682224
Pregnancy
category
  • AU: D
  • US: D (Evidence of risk)
    Routes of
    administration    		IV
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Protein binding5%
    Biological half-life36 hours
    Identifiers
    SynonymsActinomycin D
    2-Amino- 4,6-dimethyl- 3-oxo- 3H-phenoxazine- 1,9-dicarboxylic acid bis- [(5,12-diisopropyl- 9,13,16-trimethyl- 4,7,11,14,17-pentaoxo- hexadecahydro- 10-oxa- 3a,6,13,16-tetraaza- cyclopentacyclohexadecen- 8-yl)- amide]
    CAS Number
    PubChem CID
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    NIAID ChemDB
    ECHA InfoCard100.000.058
    Chemical and physical data
    FormulaC62H86N12O16
    Molar mass1255.42 g/mol
     Yes (what is this?)  (verify)
    Dactinomycin, also known as actinomycin D, is a chemotherapy medication used to treat a number of types of cancer. This includes Wilms tumor, rhabdomyosarcoma, Ewing's sarcoma, trophoblastic neoplasm, testicular cancer, and certain types of ovarian cancer. It is given by injection into a vein.[1]
    Most people develop side effects. Common side effects include bone marrow suppression, vomiting, mouth ulcers, hair loss, liver problems, infections, and muscle pains. Other serious side effects include future cancers, allergic reactions, and tissue death at the site of injection. Use in pregnancy may harm the baby.[1] Dactinomycin is in the cytotoxic antibiotic family of medications.[2] It is believed to work by blocking the creation of RNA.[1]
    Dactinomycin was approved for medical use in the United States in 1964.[1] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[3] The wholesale cost in the developing world is about 24.73 USD per 500 mcg vial.[4] It is produced from bacteria Streptomyces parvullus.[1]

    Medical use[edit]

    Actinomycin is a clear, yellow liquid administered intravenously and most commonly used in treatment of a variety of cancers, including:
    Sometimes it will be combined with other drugs in chemotherapy regimens, like the VAC regimen (with vincristine and cyclophosphamide) for treating rhabdomyosarcoma and Ewing's sarcoma.
    It is also used as a radiosensitizer in adjunct to radiotherapies, since it can increase the radiosensitivity of tumor cells by inhibiting repair of sublethal radiation damage and delay the onset of the compensatory hyperplasia that occurs following irradiation.[10]

    Side effects[edit]

    Common adverse drug reaction includes bone marrow suppression, fatigue, hair loss, mouth ulcer, loss of appetite and diarrhea. Actinomycin is a vesicant, if extravasation occurs.

    Mechanism[edit]

    In cell biology, actinomycin D is shown to have the ability to inhibit transcription. Actinomycin D does this by binding DNA at the transcription initiation complex and preventing elongation of RNA chain by RNA polymerase.[11]

    History[edit]

    Actinomycin D was the first antibiotic shown to have anti-cancer activity.[12] It was first isolated by Selman Waksman and his co-worker H. Boyd Woodruff in 1940.[13] It was approved by the U.S. Food and Drug Administration (FDA) on December 10, 1964 and launched by Merck Sharp and Dohme under the trade name Cosmegen.

    Research use[edit]

    Because actinomycin can bind DNA duplexes, it can also interfere with DNA replication, although other chemicals such as hydroxyurea are better suited for use in the laboratory as inhibitors of DNA synthesis.
    Actinomycin D and its fluorescent derivative, 7-aminoactinomycin D (7-AAD), are used as stains in microscopy and flow cytometry applications. The affinity of these stains/compounds for GC-rich regions of DNA strands makes them excellent markers for DNA. 7-AAD binds to single stranded DNA; therefore it is a useful tool in determining apoptosis and distinguishing between dead cells and live ones.[14]
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    A549 Cell

    A549 Cell Line Transfection Protocol Reagent Method

    A549 Cell Line Transfection, Protocol, Kits and Reagents

    a549 cell culturea549 cell culture
    Copyright picture from Altogen.com. Reproduced with permission from Altogen Biosystems.

    A549 Cell Line Origin

    The A549 cell line was first developed in 1972 by D.J. Giard, et al., through the removal and culturing of cancerous lung tissue in the explanted tumor of 58-year-old Caucasian male.  The cells produced were adenocarcinomic alveolar basal epithelial cells with a modal chromosome number of 66.  This type of cell in a normal lung is squamous and performs the task of diffusing water, electrolytes and other substances across the surface of the alveoli.

    A549 Cytogenetic Information

    The cell line is hypotriploid with a modal chromosome number of 66, which occurs in 24% of cells. Modal numbers of 64 and 67 is relatively common with higher ploidies occurring at an infrequent rate (0.4%).

    Morphology and Characteristics of A549 Cells

    A549 cells have been well characterized over the years and are a valuable tool to researchers that routinely use them as in vitro and in vivo models.  These cells are squamous in nature and are responsible for the diffusion of substances such as water and electrolytes across the alveoli of lungs.  These cells are human alveolar basal epithelial cells and grow adherently as a monolayer in vitro.
    A549 cells are positive for keratin, as is evidenced by immunoperoxidase staining.  The cells are able to synthesize lecithin and contain a high percentage of desaturated fatty acids, which are utilized by the cytidine-diphosphocholine pathway and important for the maintenance of membrane phospholipids in cells.

    A549 Cell Line Derived Xenograft Mouse Model

    The A549 non-small cell lung cancer (nsclc) cell line is cultured and then inoculated in mice to create the A549 CDX mouse model (cell line derived xenograft).  The A549 CDX model is one of the most highly utilized xenograft lung cancer models used by researchers for studying SoC (standard of care) and novel therapeutics (i.e. gefitinib, erlotinib, paclitaxel. lapatinib) due to overexpression of HER-2 and EGFR receptors.  Typical end of study results are comprised of tumor volume measurements, body weight tracking or animal survival.
    The following options are typically available for an A549 CDX xenograft model:
    • Dosing frequency and duration of dose administration
    • A549 Tumor Growth Delay
    • A549 Tumor Growth Inhibition
    • Dosing routes:
      • Intravenous
      • Intratracheal
      • continuous infusion
      • intraperitoneal
      • intratumoral
      • oral gavage
      • topical
      • intramuscular
      • subcutaneous
      • intranasal
      • cutting-edge micro-injection techniques and pump-controlled IV injection
    • A549 tumor immunohistochemistry
    • Cell engraftment sites
      • orthotopic transplantation
      • tail vein injection
      • left ventricular injection for metastasis studies
      • injection into mammary fat pad
      • intraperitoneal injection
    • Blood chemistry analysis
    • Toxicity and survival (optional: performing a broad health observation program)
    • Gross necropsies and histopathology
    • Imaging studies: Fluorescence-based whole body imaging, MRI
    • Positive control group employing cyclophosphamide, at a dosage of 50 mg/kg administered by intramuscular injection to the control group daily for the study duration
    • Lipid distribution and metabolic assays

    Publications

    • Chemokine production by A549 cells in response to Mycobacterium tuberculosis: In this study, A549 cells were infected with several strains of M. tuberculosis and then their chemokine production was measured. In addition, the intracellular growth of the A549 cells was measured and compared with the chemokine production. LINK: http://iai.asm.org/content/66/3/1121.long
    • Observation of differentiation in A549 cells: Monolayer cultures of A549 cells were maintained for up to three weeks, and examined using an immunoperoxidase technique. This technique used antibodies to detect surface-associated glycoproteins, which bound differently to certain A549 cells, indicating localization of the glycoproteins. LINK: http://www.ncbi.nlm.nih.gov/pubmed/6092046
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    A549 cell

    A549 cell

    From Wikipedia, the free encyclopedia

    A549 cells under DIC microscopy, from a 3-4 days old culture, showing an abundance of intercellular connections, including possible cytonemes, filopodia and other epithelial bridges. (These cells have endocytosed 25x73 nm colloidal gold nanorods.)
    A549 cells are adenocarcinomic human alveolar basal epithelial cells. The A549 cell line was first developed in 1972 by D. J. Giard, et al. through the removal and culturing of cancerous lung tissue in the explanted tumor of a 58-year-old caucasian male.[1][2] In nature, these cells are squamous and responsible for the diffusion of some substances, such as water and electrolytes, across the alveoli of lungs. If A549 cells are cultured in vitro, they grow as monolayer cells, adherent or attaching to the culture flask.[1] The human alveolar epithelial cell line A549 may be anchored or suspended in a solution in vitro.
    Another characteristic of these cells is that they are able to synthesize lecithin and contain high level of unsaturated fatty acids, which are important to maintain the membrane phospholipids in cells.[1] A549 cell line are widely used as an in vitro model for a type II pulmonary epithelial cell model for drug metabolism and as a transfection host.[3][4]
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    Wednesday, 7 June 2017

    Mānuka honey dược liệu kháng MCF7

    Evaluation of Manuka Honey Estrogen Activity Using the MCF-7 Cell ...

    Mānuka honey dược liệu kháng MCF7

    From Wikipedia, the free encyclopedia
    Five-petaled white flowers and round buds on twigs bearing short spiky leaves. A dark bee is in the centre of one of the flowers.
    A native bee visits a mānuka flower (Leptospermum scoparium)

    A bowl of mānuka honey
    Mānuka honey is a monofloral honey produced in Australia and New Zealand from the nectar of the mānuka tree. The honey is commonly sold as an alternative medicine. While a component found in mānuka honey has antibacterial properties in vitro, there is no conclusive evidence of medicinal or dietary value other than as a sweetener.

    Identification[edit]

    Mānuka honey is produced by introduced European honey bees (Apis mellifera)[1] foraging on the mānuka or tea tree (Leptospermum scoparium) which grows uncultivated throughout New Zealand and southeastern Australia.[2]
    Mānuka honey is markedly viscous, having the highest viscosity among a range of honeys.[citation needed] This property is due to the presence of a protein or colloid and is its main visually defining character, along with its typical dark cream to dark brown colour.[3][4] To be labelled New Zealand mānuka honey,[5] at least 70% of its pollen content should come from Leptospermum scoparium.[4]
    The mānuka tree flowers at the same time as Kunzea ericoides, another Myrtaceae species also called kānuka, which often shares the same growing areas. Some apiarists cannot readily differentiate these species, as both flowers have similar morphology and pollen differentiation between the two species is difficult. Therefore, melissopalynology as identification for the type of honey is valid only in association with other identification tests. In particular, L. scoparium honey is dark, whereas K. ericoides honey is pale yellow and clear, with a "delicate, sweet, slightly aromatic" aroma and a "sweet, slightly aromatic" flavour, and is not viscous.[4]
    Heather (Calluna vulgaris) honey is also viscous, but the plant flowers in late summer and its mountain distribution in north temperate Europe and central Asia does not correspond with that of Leptospermum scoparium. Therefore, its harvest cannot be mistaken for that of manuka honey.[4][clarification needed]

    Food[edit]

    Mānuka honey has a strong flavour,[3] characterised as "earthy, oily, herbaceous",[6] and "florid, rich and complex".[7] It is described by the New Zealand honey industry as having a "damp earth, heather, aromatic" aroma and a "mineral, slightly bitter" flavour.[4]

    Research[edit]

    There is insufficient evidence from existing studies to conclude that honey helps improve superficial burns or leg ulcers compared to a standard dressing.[8] Mānuka honey also does not reduce the risk of infection following treatment for ingrown toenails.[9]
    Preliminary studies indicate that methylglyoxal is an antibacterial component of mānuka honey.[10]

    Adulteration[edit]

    As a result of the high premium paid for mānuka honey, an increasing number of products now labelled as such worldwide are counterfeit or adulterated. According to research by UMFHA, the main trade association of New Zealand mānuka honey producers, whereas 1,700 tons of mānuka honey are made there annually representing almost all the world's production, some 10,000 tons of produce is being sold internationally as mānuka honey, including 1,800 tons in the UK.[11]
    In governmental agency tests in the UK between 2011 and 2013, a majority of mānuka-labelled honeys sampled lacked the non-peroxide anti-microbial activity of mānuka honey. Likewise, of 73 samples tested by UMFHA in Britain, China and Singapore in 2012-13, 43 tested negative. Separate UMFHA tests in Hong Kong found that 14 out of 56 mānuka honeys sampled had been adulterated with syrup. In 2013, the UK Food Standards Agency asked trading standards authorities to alert mānuka honey vendors to the need for legal compliance.[11]
    There is a confusing range of systems for rating the strength of mānuka honeys. In one UK chain in 2013, two products were labelled “12+ active” and “30+ total activity” respectively for “naturally occurring peroxide activity” and another “active 12+” in strength for “total phenol activity," yet none of the three was labelled for the strength of the non-peroxide antimicrobial activity specific to mānuka honey.[11]
    There have been increasing turf disputes between producers operating close to large mānuka tree clumps, and also cases reported of many hives being variously sabotaged or stolen.[12]
    One British supermarket has taken to stocking jars of the honey in tagged security cassettes, such were the losses from shoplifting.[13]
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