paclitaxel Search Results


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  • 99
    Thermo Fisher paclitaxel
    Systemic Administration of S1PR1 Modulators and S1PR1 Antagonists Block the Development of <t>Paclitaxel-induced</t> Neuropathic Pain
    Paclitaxel, supplied by Thermo Fisher, used in various techniques. Bioz Stars score: 99/100, based on 682 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    99
    Millipore paclitaxel
    Disruption of the microtubule network in frataxin-depleted hearts is prevented by <t>paclitaxel</t> and MB treatments. Hearts of 7-day-old adult male flies were dissected and double-labeled with phalloidin to stain F-actin and an anti-α-tubulin antibody. Hand-GS / + control flies were treated with DMSO (untreated) or with 10 µM paclitaxel. UAS-fhIR / +; Hand-GS / + flies were treated with DMSO (untreated), 30 µM MB or 10 µM paclitaxel. All flies were fed with RU486 during both development (40 ng/ml of food) and adulthood (100 µg/ml). Scale bar: 10 µm.
    Paclitaxel, supplied by Millipore, used in various techniques. Bioz Stars score: 99/100, based on 5933 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    92
    Bristol Myers taxol
    Examination of subcutaneous tumourigenesis and solid tumour development in nude mice. Treatment (72 hrs) of U251MG cells: control (untreated control), transfection with a plasmid vector expressing scrambled siRNA (treated control), 100 nM <t>taxol,</t> transfection with a plasmid vector expressing Bcl-2 siRNA and taxol + Bcl-2 siRNA. (A) Inhibition of subcutaneous tumourigenesis in nude mice. The U251MG cells (carrying the luciferase gene) were treated as mentioned above and the, injected under the dorsal of skin of nude mice. Beginning from day 3, the mice received intraperitoneal injection of nothing (control) or scrambled siRNA vector or taxol or Bcl-2 siRNA vector or taxol + Bcl-2 siRNA vector on alternate days for 20 days. On day 21, the mice were injected with luciferin and visualized for luciferase activity. The data are representative of six mice in each treatment group. (B) Inhibition of solid tumour development in the subcutaneous tissue of nude mice. The U251MG cells (not carrying the luciferase gene) were treated as mentioned above, harvested and suspended in an equal volume of the Matrigel, and 100 μl of this suspension (5 × 10 6 cells) was injected subcutaneously in nude mice. The animals were left for 2 weeks without any treatment. Afterwards, the mice received intraperitoneal injection of nothing (control) or scrambled siRNA vector or taxol or Bcl-2 siRNA vector or taxol + Bcl-2 siRNA vector on alternate days for 4 weeks. At the end of the sixth week, the tumours were surgically removed, weighed and photographed. (C) Longitudinal measurement of tumour volume in nude mice using a digital vernier caliper. The data are presented as mean ± S.D. of six animals in each treatment group. (D) Measurement of tumour weight following the treatments. The data are presented as mean ± S.D. of six animals in each treatment group (* P
    Taxol, supplied by Bristol Myers, used in various techniques. Bioz Stars score: 92/100, based on 393 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    95
    Celgene nab paclitaxel
    Reduced cell proliferation and increased apoptosis in RG7787 plus <t>nab-Paclitaxel-treated</t> NCI-Meso29 tumors Mice were subcutaneously inoculated with 5x10 6 NCI-Meso29 cells and the treatment was started when tumors size reached 100 mm 3 . Mice were treated with no treatment; 1 cycle of 3x 2.5mg/kg RG7787 QOD i.v.; 1 cycle of 1 x 75 mg/kg nab-Paclitaxel and 1 cycle of 3 x 25mg/kg RG7787 combined with 1 cycle 1 x 75 mg/kg nab-Paclitaxel. Representative tumor tissues from different groups were harvested after the 1 st cycle of the indicated treatments on Day 33, and representative H E staining, IHC staining for MSLN and Ki-67 expression, as well as TUNEL staining with the paraffin sections of tumor tissues were shown. Scale bar in H E, 1000 μm. Scale bar in MSLN, Ki67, TUNEL staining, 200 μm.
    Nab Paclitaxel, supplied by Celgene, used in various techniques. Bioz Stars score: 95/100, based on 1077 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    90
    Boston Scientific paclitaxel eluting stent
    (A) Diagnostic angiography showed total occlusion of the <t>paclitaxel</t> eluting stent (arrow). (B) Final angiography after thrombus aspiration and balloon dilatation of the stent showed normal antegrade flow (TIMI 3).
    Paclitaxel Eluting Stent, supplied by Boston Scientific, used in various techniques. Bioz Stars score: 90/100, based on 101 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    92
    Selleck Chemicals paclitaxel
    Effects of scheduled combinations of [DGln4]LR peptide with cDDP, <t>paclitaxel,</t> 5FU and RTX on the SQ values in 2008 and C13* cell lines. ( A ) concurrent combinations for 72 h. ( B ) Sequential combinations as described in Section 4 . The bars represent the mean of duplicate cell counts on three separate experiments and indicate the results of the inhibition of drug combinations divided by the sum of the inhibition of a single drug to obtain the values of SQ. Error bars, SD.
    Paclitaxel, supplied by Selleck Chemicals, used in various techniques. Bioz Stars score: 92/100, based on 217 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    93
    LC Laboratories paclitaxel
    Induction of polyploid multinucleated giant cancer cells through chemical inhibition of Aurora kinase signaling can serve as a strategy to identify anti-mitotic chemicals. a, Flow chart of the drug discovery project designed to identify probes selectively cytotoxic to NCI-H2122 cells. b, Proposed model for the anticipated outcome of screen identifying new anti-mitotic perturbagens. c, NCI-H2122 cells were treated with DMSO or 0.5 μM of MLN8237 and each of 12 chemical hits identified in a compound library screen. Cell viability was measured with a CellTiter-Glo assay. <t>Paclitaxel</t> was used as positive control. Structure of SW172170, the anti-mitotic candidate probe is shown. d, Cell lysates of NCI-H2122 cell line were collected 48-hours after treating with each chemical and immunoblotted to measure phosphorylated histone H3. ß-Actin was used as internal immunoblotting control. Normalized band intensities of phosphorylated Histone H3 from treated and untreated control samples are graphed. e, NCI-H2122 cells were treated with SW172170 for four days and visualized with bright-field or fluorescent microscopy. Hoechst reagent and monoclonal antibodies against Tubulin were used to visualize the nuclei and mitotic spindles, respectively (Scale bar, 25 μM).
    Paclitaxel, supplied by LC Laboratories, used in various techniques. Bioz Stars score: 93/100, based on 350 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    92
    Cytoskeleton Inc taxol
    Interfering with microtubules prevents formation of dendritic extensions by fibroblasts inside or on top of relaxed collagen matrices. ( A ) Fibroblasts were incubated 4 h in medium containing 50 ng/ml PDGF and other additions as indicated after which samples were fixed and stained for microtubules (green) and actin (red). ( Top ) Cells incubated on collagen-coated coverslips spread in an elongated, flattened morphology. Nocodazole (Noc, 5 μM) or <t>taxol</t> (5 μM) inhibited cell polarization but not spreading; cytochalasin D (Cyto D, 10 μM) inhibited spreading. ( Middle and Bottom ) Cells incubated inside or on top of relaxed collagen matrices spread by formation of dendritic extensions with microtubule cores and actin-rich tips. Nocodazole, taxol, or cytochalasin D prevented formation of dendritic extensions. ( B ) The same as A except the medium contained <t>LPA</t> instead of PDGF and incubation times were adjusted to allow for reformation of dendritic extensions. ( Top ) Cells incubated on collagen-coated coverslips spread in an elongated, flattened morphology. Nocodazole (5 μM) decreased cell polarization but not spreading; cytochalasin D (10 μM) inhibited spreading. ( Middle and Bottom ) After 4–24 h, cells incubated inside or on top of relaxed collagen matrices form bipolar extensions. Nocodazole or cytochalasin D prevented formation of extensions. (Scale bar: 50 μm.)
    Taxol, supplied by Cytoskeleton Inc, used in various techniques. Bioz Stars score: 92/100, based on 357 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    96
    Tocris paclitaxel
    Masitinib increases the cellular accumulation of [ 3 <t>H]-paclitaxel</t> and decreases the cellular efflux of [ 3 H]-paclitaxel in HEK293/ABCC10 cells. A, the accumulation of [ 3 H]-paclitaxel was measured after the cells (HEK293/pcDNA3.1 and HEK293/ABCC10) were
    Paclitaxel, supplied by Tocris, used in various techniques. Bioz Stars score: 96/100, based on 140 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    92
    Abraxis Inc nab paclitaxel
    <t>HVGGSSV-nab-paclitaxel</t> targeted to irradiated tumors a , LLC tumors grown in both hind limbs were treated with 3 Gy (left hind limb) or 0 Gy (right hind limb). Near-infrared (NIR) images acquired 72 hrs post-injection of mice after intravenous injection of Alexa fluor 750 labeled HVGGSSV-nab-paclitaxel, SGVSGHV-nab-paclitaxel, and unconjugated nab-paclitaxel. All images normalized to the same scale. Radiance was measured for both irradiated (3 Gy) and untreated (0 Gy) tumors. b , Bar graph of radiance for all treatment groups. The color scale bar indicates radiance in units of photons/s/cm 2 /sr. Shown are the mean and SEM for five animals in each group. Unpaired Student’s t test (p
    Nab Paclitaxel, supplied by Abraxis Inc, used in various techniques. Bioz Stars score: 92/100, based on 123 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    93
    FUJIFILM paclitaxel
    Effects of carboplatin and <t>paclitaxel</t> on the survival of H460 cells irradiated with X-rays or carbon-ion beams. Survival curves of cells receiving X-ray ( A ) and carbon-ion beam ( B ) irradiation. Carboplatin and paclitaxel were used at each respective IC 50 (7.9 μM and 8.3 nM). Datapoints were fitted to the linear–quadratic model. The mean ± SD is shown.
    Paclitaxel, supplied by FUJIFILM, used in various techniques. Bioz Stars score: 93/100, based on 204 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    93
    Hospira paclitaxel
    Effect of carboplatin and <t>paclitaxel</t> on TOV112D spheroids. The reference IC 50 is based on drug responses in TOV112D monolayer cultures. (a) Merged CTG-PI confocal section (image layer #13) of spheroids subjected to carboplatin and paclitaxel at different
    Paclitaxel, supplied by Hospira, used in various techniques. Bioz Stars score: 93/100, based on 193 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    93
    Teva paclitaxel
    <t>Paclitaxel</t> and anthrax toxin have additive but not synergistic anti-tumor activities. Average tumor sizes (a) and body weights (b) of mice receiving vehicle (circles), paclitaxel only (squares), PA-U2/LF only (upward triangles), or the combination (downward
    Paclitaxel, supplied by Teva, used in various techniques. Bioz Stars score: 93/100, based on 139 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    89
    Moravek Biochemicals h paclitaxel
    The effects of sipholenone E, sipholenol L and siphonellinol D on the accumulation of [ 3 <t>H]-paclitaxel</t> in KB-3-1 and KB-C2 cells The accumulation of [ 3 H]-paclitaxel was measured after preincubation with or without the reversal agents (10 μM) for 1 h at 37°C and then incubation with 0.1 μM [ 3 H]-paclitaxel in the presence or absence of the reversal agents for 2 h at 37°C. Afterwards, the cells were collected and the intracellular levels of [ 3 H]-paclitaxel were determined by scintillation counting. Verapamil was used as a positive control. Data points represent the means ± SD of triplicate determinations. Experiments were performed at least three independent times. * P
    H Paclitaxel, supplied by Moravek Biochemicals, used in various techniques. Bioz Stars score: 89/100, based on 97 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    98
    Thermo Fisher tubulin tracker green
    <t>Tubulin</t> polymerization is impaired in p35-expressing NPC-derived neural progeny following chemical microtubule disruption . For chemical disruption of microtubules, cultures were treated with 5 μg/mL nocodazole (Noc) for 3 hr, followed by washout and incubation in fresh differentiation media for 20 mins. NPC-derived neural progeny were fixed with glutaraldehyde and processed for β-tubulin immunofluorescence. (A,B) Chemically-induced disruption of microtubule structure in nocodazole-treated control NPC-derived neural progeny ( A ) was recovered by 20 mins post-washout ( B ). (C,D) Disruption of microtubule structure in nocodazole-treated p35-expressing NPC-derived neural progeny ( C ) appeared unchanged by 20 mins post-washout ( D ). (E) Quantitative image analysis of neurite outgrowth in NPC-derived neural progeny following treatment with nocodazole. Untreated control is shown for comparison to baseline neurite lengths. * p
    Tubulin Tracker Green, supplied by Thermo Fisher, used in various techniques. Bioz Stars score: 98/100, based on 191 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    92
    Cayman Chemical paclitaxel
    Viability of breast cancer cells exposed to monotherapy or with a combination therapy of <t>paclitaxel</t> with salinomycin. (A) MDA-MB-231; (B) MCF-7 cells. Mean ± SD, n = 5. * P
    Paclitaxel, supplied by Cayman Chemical, used in various techniques. Bioz Stars score: 92/100, based on 68 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    91
    Cytoskeleton Inc taxol stabilized microtubules
    <t>Taxol</t> crystals resemble asters and bundles formed in the presence of Taxol-stabilized microtubules. (A) Two asters (top and middle) and one bundle (bottom) formed in the presence of Taxol and fluorescently labeled <t>tubulin,</t> as in text. Paired images with DIC (left) and fluorescent (right) optics. (B) DIC images of a Taxol crystal aster (top) and bundle (bottom), formed in the absence of tubulin. Bars, 10 µm.
    Taxol Stabilized Microtubules, supplied by Cytoskeleton Inc, used in various techniques. Bioz Stars score: 91/100, based on 263 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    93
    LC Laboratories paclitaxel ptx
    Effects of <t>paclitaxel</t> loaded micelles on human breast tumor cell proliferation/viability determined by SRB method: a MDA-MB-231 cells. b T47D cells. Exponentially grown T47D and MDA-MB-231 cells were exposed to the different concentration of <t>PTX-loaded</t>
    Paclitaxel Ptx, supplied by LC Laboratories, used in various techniques. Bioz Stars score: 93/100, based on 33 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    93
    Oasmia Pharmaceutical paclitaxel micellar
    Plasma concentration–time curves for total <t>paclitaxel</t> at 1-h infusion of paclitaxel micellar at doses ranging between 90 and 275 mg/m 2 . a Mean concentrations for each dose level on a linear–linear scale, excluding the 90 mg dose ( n = 1) since it is outside the clinical dose range and mainly used to assess safety. b Individual (dots) and mean concentrations (continuous line) of data sets included in the PK evaluation, presented per dose level on log-linear scales. n number of data sets
    Paclitaxel Micellar, supplied by Oasmia Pharmaceutical, used in various techniques. Bioz Stars score: 93/100, based on 24 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    92
    Mayne Pharma taxol
    The anti-tumor efficacy after intraperitoneal therapy of different PTX formulations and noninvasive bioluminescence imaging in a murine model of peritoneally disseminated ovarian cancer. (A) Bioluminescence emitted by luciferase-expressing SKOV3-luc cancer cells at different time points after treatment. Peritoneal SKOV3-luc tumors bearing mice received total five intraperitoneal injection of <t>Taxol®,</t> <t>Abraxane®</t> and PTX-PEG 5k -CA 8 NPs on day 0, 4, 8, 12 and 16. Control groups received PBS only. Signal from the entire abdominal region of each mouse were quantified, and background was subtracted by measuring same sized ROIs in areas without light emission. (B) Survival of mice in different treatment groups. Open circle represents censored data point secondary to a death during anesthesia (i.e., not tumor-related). (C) Representative pseudocolor images of intraperitoneal tumor burden. Color scale minimum and maximum have been adjusted so that they are identical in each image.
    Taxol, supplied by Mayne Pharma, used in various techniques. Bioz Stars score: 92/100, based on 30 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    92
    Boston Scientific paclitaxel
    Histological evidence of delayed healing and necrotic core strut penetration in drug eluting stented saphenous vein grafts (A) A 84-year-old women received two overlapping <t>paclitaxel</t> eluting Taxus stent implanted 2 years antemortem demonstrates stent strut penetration into the lipid-rich necrotic core (NC) region. The fibrous cap (green arrow) is shown to have been disrupted by the stent struts (*-stent strut). (B) In the overlapping region, struts are uncovered but are surrounded by a thin layer of thrombus (Thr) primarily composed of fibrin. (C) In the distal region, struts are surrounded by a thin layer of thrombus.
    Paclitaxel, supplied by Boston Scientific, used in various techniques. Bioz Stars score: 92/100, based on 25 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Image Search Results


    Systemic Administration of S1PR1 Modulators and S1PR1 Antagonists Block the Development of Paclitaxel-induced Neuropathic Pain

    Journal: The Journal of Biological Chemistry

    Article Title: The Development and Maintenance of Paclitaxel-induced Neuropathic Pain Require Activation of the Sphingosine 1-Phosphate Receptor Subtype 1 *

    doi: 10.1074/jbc.M114.569574

    Figure Lengend Snippet: Systemic Administration of S1PR1 Modulators and S1PR1 Antagonists Block the Development of Paclitaxel-induced Neuropathic Pain

    Article Snippet: The tetrazolium absorption ( A 560–570 nm ) was measured from paclitaxel experiments using a Unicam UV1 spectrophotometer (Thermo Fisher Scientific) and from oxaliplatin experiments using a Glomax® multidetection system (Promega).

    Techniques: Blocking Assay

    Spinal administration of an S1PR 1 antagonist blocks the development of paclitaxel-induced neuropathic pain. Treatment with paclitaxel ( P-V , ●), but not its vehicle ( V-V , ▵), led to a time-dependent development of mechano-allodynia ( B )

    Journal: The Journal of Biological Chemistry

    Article Title: The Development and Maintenance of Paclitaxel-induced Neuropathic Pain Require Activation of the Sphingosine 1-Phosphate Receptor Subtype 1 *

    doi: 10.1074/jbc.M114.569574

    Figure Lengend Snippet: Spinal administration of an S1PR 1 antagonist blocks the development of paclitaxel-induced neuropathic pain. Treatment with paclitaxel ( P-V , ●), but not its vehicle ( V-V , ▵), led to a time-dependent development of mechano-allodynia ( B )

    Article Snippet: The tetrazolium absorption ( A 560–570 nm ) was measured from paclitaxel experiments using a Unicam UV1 spectrophotometer (Thermo Fisher Scientific) and from oxaliplatin experiments using a Glomax® multidetection system (Promega).

    Techniques:

    W146, FTY720, and NIBR-14 reverse-established paclitaxel-induced neuropathic pain. Intrathecal administration of W146 (P-W146, gray hatched bars ), but not W140 (P-W140, light gray bars ) or SEW2871 (2.2 nmol, P-SEW2871, dark gray bars ), at the time of

    Journal: The Journal of Biological Chemistry

    Article Title: The Development and Maintenance of Paclitaxel-induced Neuropathic Pain Require Activation of the Sphingosine 1-Phosphate Receptor Subtype 1 *

    doi: 10.1074/jbc.M114.569574

    Figure Lengend Snippet: W146, FTY720, and NIBR-14 reverse-established paclitaxel-induced neuropathic pain. Intrathecal administration of W146 (P-W146, gray hatched bars ), but not W140 (P-W140, light gray bars ) or SEW2871 (2.2 nmol, P-SEW2871, dark gray bars ), at the time of

    Article Snippet: The tetrazolium absorption ( A 560–570 nm ) was measured from paclitaxel experiments using a Unicam UV1 spectrophotometer (Thermo Fisher Scientific) and from oxaliplatin experiments using a Glomax® multidetection system (Promega).

    Techniques:

    Systemic delivery of S1PR 1 modulators and S1PR 1 antagonists blocks paclitaxel-induced neuropathic pain. When compared with vehicle ( V-V , ▵), treatment with paclitaxel ( P-V , ●) led to the development of mechano-hypersensitivity by D25 (

    Journal: The Journal of Biological Chemistry

    Article Title: The Development and Maintenance of Paclitaxel-induced Neuropathic Pain Require Activation of the Sphingosine 1-Phosphate Receptor Subtype 1 *

    doi: 10.1074/jbc.M114.569574

    Figure Lengend Snippet: Systemic delivery of S1PR 1 modulators and S1PR 1 antagonists blocks paclitaxel-induced neuropathic pain. When compared with vehicle ( V-V , ▵), treatment with paclitaxel ( P-V , ●) led to the development of mechano-hypersensitivity by D25 (

    Article Snippet: The tetrazolium absorption ( A 560–570 nm ) was measured from paclitaxel experiments using a Unicam UV1 spectrophotometer (Thermo Fisher Scientific) and from oxaliplatin experiments using a Glomax® multidetection system (Promega).

    Techniques:

    Spinal ceramide metabolic pathway is up-regulated during paclitaxel-induced neuropathic pain. When compared with vehicle ( V , open bars ) on D16, paclitaxel ( P , black bars ) activated ceramide metabolic pathways by enhancing SPT ( A ) and sphingomyelinase

    Journal: The Journal of Biological Chemistry

    Article Title: The Development and Maintenance of Paclitaxel-induced Neuropathic Pain Require Activation of the Sphingosine 1-Phosphate Receptor Subtype 1 *

    doi: 10.1074/jbc.M114.569574

    Figure Lengend Snippet: Spinal ceramide metabolic pathway is up-regulated during paclitaxel-induced neuropathic pain. When compared with vehicle ( V , open bars ) on D16, paclitaxel ( P , black bars ) activated ceramide metabolic pathways by enhancing SPT ( A ) and sphingomyelinase

    Article Snippet: The tetrazolium absorption ( A 560–570 nm ) was measured from paclitaxel experiments using a Unicam UV1 spectrophotometer (Thermo Fisher Scientific) and from oxaliplatin experiments using a Glomax® multidetection system (Promega).

    Techniques: Single-particle Tracking

    Inhibition of spinal neuroinflammation by the S1PR 1 antagonist W146. On D16 and when compared with vehicle ( V-V , open bars ), administration of paclitaxel (P-V, black bars ) increases cytosolic phosphorylation of NFκB p65 ( A ), nuclear translocation

    Journal: The Journal of Biological Chemistry

    Article Title: The Development and Maintenance of Paclitaxel-induced Neuropathic Pain Require Activation of the Sphingosine 1-Phosphate Receptor Subtype 1 *

    doi: 10.1074/jbc.M114.569574

    Figure Lengend Snippet: Inhibition of spinal neuroinflammation by the S1PR 1 antagonist W146. On D16 and when compared with vehicle ( V-V , open bars ), administration of paclitaxel (P-V, black bars ) increases cytosolic phosphorylation of NFκB p65 ( A ), nuclear translocation

    Article Snippet: The tetrazolium absorption ( A 560–570 nm ) was measured from paclitaxel experiments using a Unicam UV1 spectrophotometer (Thermo Fisher Scientific) and from oxaliplatin experiments using a Glomax® multidetection system (Promega).

    Techniques: Inhibition, Translocation Assay

    FTY720, CYM5442, and NIBR-14 reverse established paclitaxel-induced neuropathic pain without altering acute pain. A, miniosmotic pumps implanted subcutaneously on D16 followed by a single loading dose of either FTY720 (P-FTY720, 0.1 mg/kg/day, ■),

    Journal: The Journal of Biological Chemistry

    Article Title: The Development and Maintenance of Paclitaxel-induced Neuropathic Pain Require Activation of the Sphingosine 1-Phosphate Receptor Subtype 1 *

    doi: 10.1074/jbc.M114.569574

    Figure Lengend Snippet: FTY720, CYM5442, and NIBR-14 reverse established paclitaxel-induced neuropathic pain without altering acute pain. A, miniosmotic pumps implanted subcutaneously on D16 followed by a single loading dose of either FTY720 (P-FTY720, 0.1 mg/kg/day, ■),

    Article Snippet: The tetrazolium absorption ( A 560–570 nm ) was measured from paclitaxel experiments using a Unicam UV1 spectrophotometer (Thermo Fisher Scientific) and from oxaliplatin experiments using a Glomax® multidetection system (Promega).

    Techniques:

    Systemic delivery of S1PR 1 modulators and S1PR 1 antagonists blocks paclitaxel-induced pro-inflammatory cytokine production in spinal cord. As compared with vehicle ( V-V , open bars ), paclitaxel ( P-V , black bars )-induced increases in the production of proinflammatory

    Journal: The Journal of Biological Chemistry

    Article Title: The Development and Maintenance of Paclitaxel-induced Neuropathic Pain Require Activation of the Sphingosine 1-Phosphate Receptor Subtype 1 *

    doi: 10.1074/jbc.M114.569574

    Figure Lengend Snippet: Systemic delivery of S1PR 1 modulators and S1PR 1 antagonists blocks paclitaxel-induced pro-inflammatory cytokine production in spinal cord. As compared with vehicle ( V-V , open bars ), paclitaxel ( P-V , black bars )-induced increases in the production of proinflammatory

    Article Snippet: The tetrazolium absorption ( A 560–570 nm ) was measured from paclitaxel experiments using a Unicam UV1 spectrophotometer (Thermo Fisher Scientific) and from oxaliplatin experiments using a Glomax® multidetection system (Promega).

    Techniques:

    S1PR1 Modulators and S1PR1 Antagonists, but Not S1PR1 Agonists, Reverse Established Paclitaxel-induced Neuropathic Pain in a Naloxone-independent Manner

    Journal: The Journal of Biological Chemistry

    Article Title: The Development and Maintenance of Paclitaxel-induced Neuropathic Pain Require Activation of the Sphingosine 1-Phosphate Receptor Subtype 1 *

    doi: 10.1074/jbc.M114.569574

    Figure Lengend Snippet: S1PR1 Modulators and S1PR1 Antagonists, but Not S1PR1 Agonists, Reverse Established Paclitaxel-induced Neuropathic Pain in a Naloxone-independent Manner

    Article Snippet: The tetrazolium absorption ( A 560–570 nm ) was measured from paclitaxel experiments using a Unicam UV1 spectrophotometer (Thermo Fisher Scientific) and from oxaliplatin experiments using a Glomax® multidetection system (Promega).

    Techniques:

    Activation of NFκB and MAPK activation in spinal cord following paclitaxel treatment. On D16 and when compared with vehicle ( V-V , open bars ), administration of paclitaxel ( P-V , black bars ) increased the phosphorylation of cytosolic p65 ( A ), nuclear

    Journal: The Journal of Biological Chemistry

    Article Title: The Development and Maintenance of Paclitaxel-induced Neuropathic Pain Require Activation of the Sphingosine 1-Phosphate Receptor Subtype 1 *

    doi: 10.1074/jbc.M114.569574

    Figure Lengend Snippet: Activation of NFκB and MAPK activation in spinal cord following paclitaxel treatment. On D16 and when compared with vehicle ( V-V , open bars ), administration of paclitaxel ( P-V , black bars ) increased the phosphorylation of cytosolic p65 ( A ), nuclear

    Article Snippet: The tetrazolium absorption ( A 560–570 nm ) was measured from paclitaxel experiments using a Unicam UV1 spectrophotometer (Thermo Fisher Scientific) and from oxaliplatin experiments using a Glomax® multidetection system (Promega).

    Techniques: Activation Assay

    Spinal administration of SK-I blocks ceramide metabolic pathway and paclitaxel-induced neuropathic pain. When compared with vehicle ( V , open bars ) on D16, paclitaxel ( P , black bars ) activated ceramide metabolic pathways by increasing SphK1 activity (

    Journal: The Journal of Biological Chemistry

    Article Title: The Development and Maintenance of Paclitaxel-induced Neuropathic Pain Require Activation of the Sphingosine 1-Phosphate Receptor Subtype 1 *

    doi: 10.1074/jbc.M114.569574

    Figure Lengend Snippet: Spinal administration of SK-I blocks ceramide metabolic pathway and paclitaxel-induced neuropathic pain. When compared with vehicle ( V , open bars ) on D16, paclitaxel ( P , black bars ) activated ceramide metabolic pathways by increasing SphK1 activity (

    Article Snippet: The tetrazolium absorption ( A 560–570 nm ) was measured from paclitaxel experiments using a Unicam UV1 spectrophotometer (Thermo Fisher Scientific) and from oxaliplatin experiments using a Glomax® multidetection system (Promega).

    Techniques: Activity Assay

    Disruption of the microtubule network in frataxin-depleted hearts is prevented by paclitaxel and MB treatments. Hearts of 7-day-old adult male flies were dissected and double-labeled with phalloidin to stain F-actin and an anti-α-tubulin antibody. Hand-GS / + control flies were treated with DMSO (untreated) or with 10 µM paclitaxel. UAS-fhIR / +; Hand-GS / + flies were treated with DMSO (untreated), 30 µM MB or 10 µM paclitaxel. All flies were fed with RU486 during both development (40 ng/ml of food) and adulthood (100 µg/ml). Scale bar: 10 µm.

    Journal: Disease Models & Mechanisms

    Article Title: Identification of cardioprotective drugs by medium-scale in vivo pharmacological screening on a Drosophila cardiac model of Friedreich's ataxia

    doi: 10.1242/dmm.033811

    Figure Lengend Snippet: Disruption of the microtubule network in frataxin-depleted hearts is prevented by paclitaxel and MB treatments. Hearts of 7-day-old adult male flies were dissected and double-labeled with phalloidin to stain F-actin and an anti-α-tubulin antibody. Hand-GS / + control flies were treated with DMSO (untreated) or with 10 µM paclitaxel. UAS-fhIR / +; Hand-GS / + flies were treated with DMSO (untreated), 30 µM MB or 10 µM paclitaxel. All flies were fed with RU486 during both development (40 ng/ml of food) and adulthood (100 µg/ml). Scale bar: 10 µm.

    Article Snippet: Paclitaxel (semi-synthetic, Sigma) and MB (Sigma) were used for dose-response assays and histological studies.

    Techniques: Labeling, Staining

    The actin and myosin networks are affected by frataxin depletion in cardiomyocytes and improved by paclitaxel and MB treatments. Hearts of 3- to 5-day-old adult male flies were dissected and double-labeled with phalloidin to stain F-actin and an anti-GFP antibody to stain the MHC-GFP fusion protein. MHC:GFP / +; Hand-GS / + control flies were treated with DMSO (i.e. untreated; top row). MHC:GFP / UAS-fhIR; Hand-GS / + flies were treated with DMSO (untreated), 30 µM MB or 10 µM paclitaxel. All flies were fed with RU486 during both development (40 ng/ml of food) and adulthood (100 µg/ml). Scale bar: 10 µm.

    Journal: Disease Models & Mechanisms

    Article Title: Identification of cardioprotective drugs by medium-scale in vivo pharmacological screening on a Drosophila cardiac model of Friedreich's ataxia

    doi: 10.1242/dmm.033811

    Figure Lengend Snippet: The actin and myosin networks are affected by frataxin depletion in cardiomyocytes and improved by paclitaxel and MB treatments. Hearts of 3- to 5-day-old adult male flies were dissected and double-labeled with phalloidin to stain F-actin and an anti-GFP antibody to stain the MHC-GFP fusion protein. MHC:GFP / +; Hand-GS / + control flies were treated with DMSO (i.e. untreated; top row). MHC:GFP / UAS-fhIR; Hand-GS / + flies were treated with DMSO (untreated), 30 µM MB or 10 µM paclitaxel. All flies were fed with RU486 during both development (40 ng/ml of food) and adulthood (100 µg/ml). Scale bar: 10 µm.

    Article Snippet: Paclitaxel (semi-synthetic, Sigma) and MB (Sigma) were used for dose-response assays and histological studies.

    Techniques: Labeling, Staining

    Dose-dependent effect of paclitaxel treatment on cardiac function of frataxin-deficient hearts. (A) Representative M-modes (generated by horizontal alignment of rows extracted at the same position for each movie frame) of control UAS-mitoGFP / +; Hand-GS / + (+) flies, untreated or treated with 10 µM paclitaxel, and of UAS-mitoGFP / UAS-fhIR; Hand-GS / + (fhIR) flies, untreated or treated with 5 µM or 10 µM paclitaxel. Scale bar: 1 s. (B-D) End-systolic diameter (ESD, µm), fractional shortening (FS, %) and end-diastolic diameter (EDD, µm) of + control flies, treated with DMSO ( n =17), or with 1 µM ( n =15), 5 µM ( n =10) or 10 µM paclitaxel ( n =5), and of fhIR flies treated with DMSO ( n =19), or with 1 µM ( n =22), 5 µM ( n =15), 10 µM paclitaxel ( n =10), or with 10 µM ( n =18) or 30 µM Methylene Blue (MB; n =20). All flies were 4 days old and fed with RU486 during both development (40 ng/ml of food) and adulthood (100 µg/ml). All values are means (±s.e.m.). Statistical significance was assessed by non-parametric Wilcoxon analysis. Significant differences between treated and untreated flies of the same genotype are indicated: * P

    Journal: Disease Models & Mechanisms

    Article Title: Identification of cardioprotective drugs by medium-scale in vivo pharmacological screening on a Drosophila cardiac model of Friedreich's ataxia

    doi: 10.1242/dmm.033811

    Figure Lengend Snippet: Dose-dependent effect of paclitaxel treatment on cardiac function of frataxin-deficient hearts. (A) Representative M-modes (generated by horizontal alignment of rows extracted at the same position for each movie frame) of control UAS-mitoGFP / +; Hand-GS / + (+) flies, untreated or treated with 10 µM paclitaxel, and of UAS-mitoGFP / UAS-fhIR; Hand-GS / + (fhIR) flies, untreated or treated with 5 µM or 10 µM paclitaxel. Scale bar: 1 s. (B-D) End-systolic diameter (ESD, µm), fractional shortening (FS, %) and end-diastolic diameter (EDD, µm) of + control flies, treated with DMSO ( n =17), or with 1 µM ( n =15), 5 µM ( n =10) or 10 µM paclitaxel ( n =5), and of fhIR flies treated with DMSO ( n =19), or with 1 µM ( n =22), 5 µM ( n =15), 10 µM paclitaxel ( n =10), or with 10 µM ( n =18) or 30 µM Methylene Blue (MB; n =20). All flies were 4 days old and fed with RU486 during both development (40 ng/ml of food) and adulthood (100 µg/ml). All values are means (±s.e.m.). Statistical significance was assessed by non-parametric Wilcoxon analysis. Significant differences between treated and untreated flies of the same genotype are indicated: * P

    Article Snippet: Paclitaxel (semi-synthetic, Sigma) and MB (Sigma) were used for dose-response assays and histological studies.

    Techniques: Generated

    The sarcomeric pattern of Sallimus is modified in frataxin-depleted hearts, and improved by paclitaxel and MB treatments. Hearts of 3- to 5-day-old adult male flies were dissected and double-labeled with phalloidin to stain F-actin and an anti-GFP antibody to stain the Sls-GFP fusion protein. Hand-GS / sls:GFP control flies were treated with DMSO (i.e. untreated; top row). UAS-fhIR / +; Hand-GS / sls:GFP flies were treated with DMSO (untreated), 30 µM MB or 10 µM paclitaxel. All flies were fed with RU486 during both development (40 ng/ml of food) and adulthood (100 µg/ml). Scale bar: 10 µm.

    Journal: Disease Models & Mechanisms

    Article Title: Identification of cardioprotective drugs by medium-scale in vivo pharmacological screening on a Drosophila cardiac model of Friedreich's ataxia

    doi: 10.1242/dmm.033811

    Figure Lengend Snippet: The sarcomeric pattern of Sallimus is modified in frataxin-depleted hearts, and improved by paclitaxel and MB treatments. Hearts of 3- to 5-day-old adult male flies were dissected and double-labeled with phalloidin to stain F-actin and an anti-GFP antibody to stain the Sls-GFP fusion protein. Hand-GS / sls:GFP control flies were treated with DMSO (i.e. untreated; top row). UAS-fhIR / +; Hand-GS / sls:GFP flies were treated with DMSO (untreated), 30 µM MB or 10 µM paclitaxel. All flies were fed with RU486 during both development (40 ng/ml of food) and adulthood (100 µg/ml). Scale bar: 10 µm.

    Article Snippet: Paclitaxel (semi-synthetic, Sigma) and MB (Sigma) were used for dose-response assays and histological studies.

    Techniques: Modification, Labeling, Staining

    Effects of MPSP-001 on mitotic spindle formation and tubulin disruption. (A) Illust rations of the effects of MPSP-001 on the mitotic spindle in HeLa cells (e-h) using immuno-fluorescence microscopy technique. HeLa cells grown in log phase were treated with 5 μmol/L MPSP-001 for 16 h, followed by fixation and immunofluorescence staining for tubulin (white) and DNA (blue). Examples of a normal interphase (a), normal prometaphase (b), normal metaphase (c) and normal telophase (d) were shown. Examples of a damaged interphase (e) and various forms of abnormal mitoses include a tripolar prometaphase (f), a mutipolar metaphase (g) and an abnormal bipolar metaphase with lagging chromosomes or chromosomes not aligned to the metaphase plate (h) were shown (×600). (B) Statistical analysis of the effects of MPSP-001 on the mitotic spindles in HeLa cells. (C) Disruption of tubulin by MPSP-001, colchicine, and paclitaxel in HeLa cells and tubulin-GFP-HeLa cells (over-expression of the fusion protein of tubulin and GFP). HeLa cells and tubulin-GFP-HeLa cells grown in log phase were treated with 0.1% DMSO (a, f), 250 nmol/L Taxol (b, g), 100 nmol/L colchicine (c, h), 100 nmol/L vincristine (d, i) and 5 μmol/L MPSP-001 for 16 h, followed by fixation and immunofluorescence staining for tubulin (In Tubulin-GFP-HeLa cells, immunofluorescence staining was omitted) .Then the morphology of interphase tubulin (white) was observed (×600).

    Journal: Acta Pharmacologica Sinica

    Article Title: A novel sulfonamide agent, MPSP-001, exhibits potent activity against human cancer cells in vitro through disruption of microtubule

    doi: 10.1038/aps.2011.156

    Figure Lengend Snippet: Effects of MPSP-001 on mitotic spindle formation and tubulin disruption. (A) Illust rations of the effects of MPSP-001 on the mitotic spindle in HeLa cells (e-h) using immuno-fluorescence microscopy technique. HeLa cells grown in log phase were treated with 5 μmol/L MPSP-001 for 16 h, followed by fixation and immunofluorescence staining for tubulin (white) and DNA (blue). Examples of a normal interphase (a), normal prometaphase (b), normal metaphase (c) and normal telophase (d) were shown. Examples of a damaged interphase (e) and various forms of abnormal mitoses include a tripolar prometaphase (f), a mutipolar metaphase (g) and an abnormal bipolar metaphase with lagging chromosomes or chromosomes not aligned to the metaphase plate (h) were shown (×600). (B) Statistical analysis of the effects of MPSP-001 on the mitotic spindles in HeLa cells. (C) Disruption of tubulin by MPSP-001, colchicine, and paclitaxel in HeLa cells and tubulin-GFP-HeLa cells (over-expression of the fusion protein of tubulin and GFP). HeLa cells and tubulin-GFP-HeLa cells grown in log phase were treated with 0.1% DMSO (a, f), 250 nmol/L Taxol (b, g), 100 nmol/L colchicine (c, h), 100 nmol/L vincristine (d, i) and 5 μmol/L MPSP-001 for 16 h, followed by fixation and immunofluorescence staining for tubulin (In Tubulin-GFP-HeLa cells, immunofluorescence staining was omitted) .Then the morphology of interphase tubulin (white) was observed (×600).

    Article Snippet: Chemicals and antibodies Colchicine (COL), paclitaxel (Taxol), vincristin (VCR) and Adriamycin (ADR) were purchased from Sigma Chemical Co. Antibodies were obtained from following companies: poly(ADP-ribose) polymerase (PARP) (Cell Signalling Technology); α-tubulin, horseradish peroxidase (HRP)-conjugated secondary antibody (Santa Cruz Biotechnology); and fluorescent isothiocyanate (FITC)-conjugated secondary antibody (Ancell Corporation).

    Techniques: Fluorescence, Microscopy, Immunofluorescence, Staining, Over Expression

    Effects of MPSP-001 on in vitro tubulin polymerization and competitive binding of colchicine site. (A) Effects of MPSP-001 (25 μmol/L, 100 μmol/L), Taxol (10 μmol/L), colchicines (10 μmol/L) and vincristine (10 μmol/L) on bovine brain tubulin polymerization were measured turbidimetrically. Changes in absorbance at 340 nm (A340) were measured and plotted as a function of time. (B) MPSP-001 binding to tubulin directly and inhibiting tubulin polymerization. Tubulin was co-incubated with indicated concentrations of VCR and MPSP-001 for 1 h, then 5 μmol/L colchicine was added. The fluorescence was measured by spectrofluorometer. All assays were repeated twice and representative data were shown. (C) Interactions between α,β-tubulin and compound MPSP-001 in the docking complex in 3D pattern. Tubulin was shown in cartoon style with the β and α subunit colored in green and cyan, respectively; compound MPSP-001 was shown in stick style; the residues within 4 Å around compound MPSP-001 were shown in line style. Magenta dashed lines denoted the potential hydrogen bonds. (D) 2D representation were drawn using LIGPLOT. Dashed lines represented hydrogen bonds and spiked residues form hydrophobic contacts with the compound.

    Journal: Acta Pharmacologica Sinica

    Article Title: A novel sulfonamide agent, MPSP-001, exhibits potent activity against human cancer cells in vitro through disruption of microtubule

    doi: 10.1038/aps.2011.156

    Figure Lengend Snippet: Effects of MPSP-001 on in vitro tubulin polymerization and competitive binding of colchicine site. (A) Effects of MPSP-001 (25 μmol/L, 100 μmol/L), Taxol (10 μmol/L), colchicines (10 μmol/L) and vincristine (10 μmol/L) on bovine brain tubulin polymerization were measured turbidimetrically. Changes in absorbance at 340 nm (A340) were measured and plotted as a function of time. (B) MPSP-001 binding to tubulin directly and inhibiting tubulin polymerization. Tubulin was co-incubated with indicated concentrations of VCR and MPSP-001 for 1 h, then 5 μmol/L colchicine was added. The fluorescence was measured by spectrofluorometer. All assays were repeated twice and representative data were shown. (C) Interactions between α,β-tubulin and compound MPSP-001 in the docking complex in 3D pattern. Tubulin was shown in cartoon style with the β and α subunit colored in green and cyan, respectively; compound MPSP-001 was shown in stick style; the residues within 4 Å around compound MPSP-001 were shown in line style. Magenta dashed lines denoted the potential hydrogen bonds. (D) 2D representation were drawn using LIGPLOT. Dashed lines represented hydrogen bonds and spiked residues form hydrophobic contacts with the compound.

    Article Snippet: Chemicals and antibodies Colchicine (COL), paclitaxel (Taxol), vincristin (VCR) and Adriamycin (ADR) were purchased from Sigma Chemical Co. Antibodies were obtained from following companies: poly(ADP-ribose) polymerase (PARP) (Cell Signalling Technology); α-tubulin, horseradish peroxidase (HRP)-conjugated secondary antibody (Santa Cruz Biotechnology); and fluorescent isothiocyanate (FITC)-conjugated secondary antibody (Ancell Corporation).

    Techniques: In Vitro, Binding Assay, Incubation, Fluorescence

    Synergistic effects of MPSP-001 in combination with colchicine and Taxol on blocking mitosis. (A) Flow cytometry analysis of the mitosis block effects using different concentrations of MPSP-001, colchicines and Taxol. HeLa cells were incubated with different concentrations of MPSP-001, colchicines and taxol for 16 h. Then cells were fixed and stained with PI and analyzed by flow cytometry. The G 2 /M distribution values were graphed. Data are the means of triplicates±SD. (B) Flow cytometry analysis of the effects of taxol (25 nmol/L), colchicine (10 nmol/L), MPSP-001 (1 μmol/L) or the combination of Taxol+MPSP-001 and colchicines+MPSP-001 on cell cycle distribution. HeLa cells were incubated with drugs for 16 h. The cells were then fixed and stained with PI and analyzed by flow cytometry.

    Journal: Acta Pharmacologica Sinica

    Article Title: A novel sulfonamide agent, MPSP-001, exhibits potent activity against human cancer cells in vitro through disruption of microtubule

    doi: 10.1038/aps.2011.156

    Figure Lengend Snippet: Synergistic effects of MPSP-001 in combination with colchicine and Taxol on blocking mitosis. (A) Flow cytometry analysis of the mitosis block effects using different concentrations of MPSP-001, colchicines and Taxol. HeLa cells were incubated with different concentrations of MPSP-001, colchicines and taxol for 16 h. Then cells were fixed and stained with PI and analyzed by flow cytometry. The G 2 /M distribution values were graphed. Data are the means of triplicates±SD. (B) Flow cytometry analysis of the effects of taxol (25 nmol/L), colchicine (10 nmol/L), MPSP-001 (1 μmol/L) or the combination of Taxol+MPSP-001 and colchicines+MPSP-001 on cell cycle distribution. HeLa cells were incubated with drugs for 16 h. The cells were then fixed and stained with PI and analyzed by flow cytometry.

    Article Snippet: Chemicals and antibodies Colchicine (COL), paclitaxel (Taxol), vincristin (VCR) and Adriamycin (ADR) were purchased from Sigma Chemical Co. Antibodies were obtained from following companies: poly(ADP-ribose) polymerase (PARP) (Cell Signalling Technology); α-tubulin, horseradish peroxidase (HRP)-conjugated secondary antibody (Santa Cruz Biotechnology); and fluorescent isothiocyanate (FITC)-conjugated secondary antibody (Ancell Corporation).

    Techniques: Blocking Assay, Flow Cytometry, Cytometry, Incubation, Staining

    Morphology changes and neural markers are regulated differentially. a Appearance of neuron-like morphology of MSCs induced with 10 μM forskolin and 100 μM IBMX (FI) for 1 h. b Cell morphology of MSCs induced with FI in the presence of 0.4 μM microtubule stabilizer paclitaxel (Ptx) for 1 h. c – d Expression of neural markers, NSE, Tuj1, and GFAP, in control cells, cells induced with FI for 1 day in the absence or presence of Ptx ( n = 3). For the FI treatment, cells were treated with FI or FI plus Ptx for 3 h and then changed to fresh FI media to reduce toxicity from Ptx treatment. * p

    Journal: Cellular and molecular life sciences : CMLS

    Article Title: cAMP initiates early phase neuron-like morphology changes and late phase neural differentiation in mesenchymal stem cells

    doi: 10.1007/s00018-010-0497-1

    Figure Lengend Snippet: Morphology changes and neural markers are regulated differentially. a Appearance of neuron-like morphology of MSCs induced with 10 μM forskolin and 100 μM IBMX (FI) for 1 h. b Cell morphology of MSCs induced with FI in the presence of 0.4 μM microtubule stabilizer paclitaxel (Ptx) for 1 h. c – d Expression of neural markers, NSE, Tuj1, and GFAP, in control cells, cells induced with FI for 1 day in the absence or presence of Ptx ( n = 3). For the FI treatment, cells were treated with FI or FI plus Ptx for 3 h and then changed to fresh FI media to reduce toxicity from Ptx treatment. * p

    Article Snippet: Paclitaxel (Ptx) (Sigma) was used to stabilize microtubules at concentration of 0.4 uM.

    Techniques: Expressing

    Examination of subcutaneous tumourigenesis and solid tumour development in nude mice. Treatment (72 hrs) of U251MG cells: control (untreated control), transfection with a plasmid vector expressing scrambled siRNA (treated control), 100 nM taxol, transfection with a plasmid vector expressing Bcl-2 siRNA and taxol + Bcl-2 siRNA. (A) Inhibition of subcutaneous tumourigenesis in nude mice. The U251MG cells (carrying the luciferase gene) were treated as mentioned above and the, injected under the dorsal of skin of nude mice. Beginning from day 3, the mice received intraperitoneal injection of nothing (control) or scrambled siRNA vector or taxol or Bcl-2 siRNA vector or taxol + Bcl-2 siRNA vector on alternate days for 20 days. On day 21, the mice were injected with luciferin and visualized for luciferase activity. The data are representative of six mice in each treatment group. (B) Inhibition of solid tumour development in the subcutaneous tissue of nude mice. The U251MG cells (not carrying the luciferase gene) were treated as mentioned above, harvested and suspended in an equal volume of the Matrigel, and 100 μl of this suspension (5 × 10 6 cells) was injected subcutaneously in nude mice. The animals were left for 2 weeks without any treatment. Afterwards, the mice received intraperitoneal injection of nothing (control) or scrambled siRNA vector or taxol or Bcl-2 siRNA vector or taxol + Bcl-2 siRNA vector on alternate days for 4 weeks. At the end of the sixth week, the tumours were surgically removed, weighed and photographed. (C) Longitudinal measurement of tumour volume in nude mice using a digital vernier caliper. The data are presented as mean ± S.D. of six animals in each treatment group. (D) Measurement of tumour weight following the treatments. The data are presented as mean ± S.D. of six animals in each treatment group (* P

    Journal: Journal of Cellular and Molecular Medicine

    Article Title: Combination of taxol and Bcl-2 siRNA induces apoptosis in human glioblastoma cells and inhibits invasion, angiogenesis and tumour growth

    doi: 10.1111/j.1582-4934.2008.00539.x

    Figure Lengend Snippet: Examination of subcutaneous tumourigenesis and solid tumour development in nude mice. Treatment (72 hrs) of U251MG cells: control (untreated control), transfection with a plasmid vector expressing scrambled siRNA (treated control), 100 nM taxol, transfection with a plasmid vector expressing Bcl-2 siRNA and taxol + Bcl-2 siRNA. (A) Inhibition of subcutaneous tumourigenesis in nude mice. The U251MG cells (carrying the luciferase gene) were treated as mentioned above and the, injected under the dorsal of skin of nude mice. Beginning from day 3, the mice received intraperitoneal injection of nothing (control) or scrambled siRNA vector or taxol or Bcl-2 siRNA vector or taxol + Bcl-2 siRNA vector on alternate days for 20 days. On day 21, the mice were injected with luciferin and visualized for luciferase activity. The data are representative of six mice in each treatment group. (B) Inhibition of solid tumour development in the subcutaneous tissue of nude mice. The U251MG cells (not carrying the luciferase gene) were treated as mentioned above, harvested and suspended in an equal volume of the Matrigel, and 100 μl of this suspension (5 × 10 6 cells) was injected subcutaneously in nude mice. The animals were left for 2 weeks without any treatment. Afterwards, the mice received intraperitoneal injection of nothing (control) or scrambled siRNA vector or taxol or Bcl-2 siRNA vector or taxol + Bcl-2 siRNA vector on alternate days for 4 weeks. At the end of the sixth week, the tumours were surgically removed, weighed and photographed. (C) Longitudinal measurement of tumour volume in nude mice using a digital vernier caliper. The data are presented as mean ± S.D. of six animals in each treatment group. (D) Measurement of tumour weight following the treatments. The data are presented as mean ± S.D. of six animals in each treatment group (* P

    Article Snippet: Taxol (also known as paclitaxel, 6 mg/ml) was procured from Bristol-Myers Squibb (Princeton, NJ, USA) and diluted to a 1-mM solution in dimethylsulfoxide and protected from light.

    Techniques: Mouse Assay, Transfection, Plasmid Preparation, Expressing, Inhibition, Luciferase, Injection, Activity Assay

    Longitudinal bioluminescence imaging of intracranial tumour growth in nude mice. The U251MG cells (1 × 10 6 ) stably transfected with luciferase gene were used for treatments and implantations in nude mice. Treatment (72 hrs) of U251MG cells: control (untreated control), transfection with a plasmid vector expressing scrambled siRNA (treated control), 100 nM taxol, transfection with a plasmid vector expressing Bcl-2 siRNA and taxol + Bcl-2 siRNA. The cells from each treatment were harvested and 1 × 10 6 cells were suspended in 10 μl of serum-free medium and injected into the cerebrum of nude mice with the help of a stereotaxic apparatus. On day 3 onwards, the mice were injected intraperitoneally with nothing (control) or scrambled siRNA vector (treated control) or taxol or Bcl-2 siRNA vector or taxol + Bcl-2 siRNA vector for 20 days on alternate days. On days 7, 14 and 21, the mice were injected with luciferin for visualization of bioluminescence from luciferase activity to detect the extent of intracranial tumour growth in nude mice. The data are representative of six mice in each treatment group.

    Journal: Journal of Cellular and Molecular Medicine

    Article Title: Combination of taxol and Bcl-2 siRNA induces apoptosis in human glioblastoma cells and inhibits invasion, angiogenesis and tumour growth

    doi: 10.1111/j.1582-4934.2008.00539.x

    Figure Lengend Snippet: Longitudinal bioluminescence imaging of intracranial tumour growth in nude mice. The U251MG cells (1 × 10 6 ) stably transfected with luciferase gene were used for treatments and implantations in nude mice. Treatment (72 hrs) of U251MG cells: control (untreated control), transfection with a plasmid vector expressing scrambled siRNA (treated control), 100 nM taxol, transfection with a plasmid vector expressing Bcl-2 siRNA and taxol + Bcl-2 siRNA. The cells from each treatment were harvested and 1 × 10 6 cells were suspended in 10 μl of serum-free medium and injected into the cerebrum of nude mice with the help of a stereotaxic apparatus. On day 3 onwards, the mice were injected intraperitoneally with nothing (control) or scrambled siRNA vector (treated control) or taxol or Bcl-2 siRNA vector or taxol + Bcl-2 siRNA vector for 20 days on alternate days. On days 7, 14 and 21, the mice were injected with luciferin for visualization of bioluminescence from luciferase activity to detect the extent of intracranial tumour growth in nude mice. The data are representative of six mice in each treatment group.

    Article Snippet: Taxol (also known as paclitaxel, 6 mg/ml) was procured from Bristol-Myers Squibb (Princeton, NJ, USA) and diluted to a 1-mM solution in dimethylsulfoxide and protected from light.

    Techniques: Imaging, Mouse Assay, Stable Transfection, Transfection, Luciferase, Plasmid Preparation, Expressing, Injection, Activity Assay

    In vitro Matrigel invasion assay using U138MG and U251MG cells. Treatment (72 hrs) of cells: transfection with a plasmid vector expressing scrambled siRNA (treated control), 100 nM taxol, transfection with a plasmid vector expressing Bcl-2 siRNA and taxol + Bcl-2 siRNA. Invasion assays were carried out in 12-well transwell inserts of polycarbonate filters. After 48 hrs incubation at 37°C in a CO 2 incubator, the membranes were collected and stained with HEMA. The number of cells that migrated to the undersurface of the membrane were examined under a microscope, counted and photographed. (A) The changes in capability of invasion of U138MG cells after the treatments. (B) Quantitative evaluation of invading U138MG cells. (C) The changes in capability of invasion of U251MG cells after the treatments. (D) Quantitative evaluation of invading U251MG cells. The quantitative data are presented as mean ± S.D. of cells from 10 randomly selected microscopic fields from three independent wells (* P

    Journal: Journal of Cellular and Molecular Medicine

    Article Title: Combination of taxol and Bcl-2 siRNA induces apoptosis in human glioblastoma cells and inhibits invasion, angiogenesis and tumour growth

    doi: 10.1111/j.1582-4934.2008.00539.x

    Figure Lengend Snippet: In vitro Matrigel invasion assay using U138MG and U251MG cells. Treatment (72 hrs) of cells: transfection with a plasmid vector expressing scrambled siRNA (treated control), 100 nM taxol, transfection with a plasmid vector expressing Bcl-2 siRNA and taxol + Bcl-2 siRNA. Invasion assays were carried out in 12-well transwell inserts of polycarbonate filters. After 48 hrs incubation at 37°C in a CO 2 incubator, the membranes were collected and stained with HEMA. The number of cells that migrated to the undersurface of the membrane were examined under a microscope, counted and photographed. (A) The changes in capability of invasion of U138MG cells after the treatments. (B) Quantitative evaluation of invading U138MG cells. (C) The changes in capability of invasion of U251MG cells after the treatments. (D) Quantitative evaluation of invading U251MG cells. The quantitative data are presented as mean ± S.D. of cells from 10 randomly selected microscopic fields from three independent wells (* P

    Article Snippet: Taxol (also known as paclitaxel, 6 mg/ml) was procured from Bristol-Myers Squibb (Princeton, NJ, USA) and diluted to a 1-mM solution in dimethylsulfoxide and protected from light.

    Techniques: In Vitro, Invasion Assay, Transfection, Plasmid Preparation, Expressing, Incubation, Staining, Microscopy

    FACS analysis for detection of apoptotic cells and DNA fragmentation. Treatment (72 hrs) of cells: transfection with a plasmid vector expressing scrambled siRNA (treated control), 100 nM taxol, transfection with a plasmid vector expressing Bcl-2 siRNA and taxol + Bcl-2 siRNA. (A) FACS dot plots of U251MG cells. Before FACS analysis, the cells were treated with 50 μg/ml propidium iodide for 30 min. at 4°C in dark. Population in the M1 area represents the apoptotic/dead cells. (B) FACS histograms of U251MG cells. The prominent increase in population of cells in the sub-G1 phase (M1) indicated increase in apoptosis after treatment with taxol or Bcl-2 siRNA or both. (C) Quantitative presentation of DNA fragmentation data from FACS analysis to indicate percent changes in live and apoptotic cells. Data are representative of four independent experiments (* P

    Journal: Journal of Cellular and Molecular Medicine

    Article Title: Combination of taxol and Bcl-2 siRNA induces apoptosis in human glioblastoma cells and inhibits invasion, angiogenesis and tumour growth

    doi: 10.1111/j.1582-4934.2008.00539.x

    Figure Lengend Snippet: FACS analysis for detection of apoptotic cells and DNA fragmentation. Treatment (72 hrs) of cells: transfection with a plasmid vector expressing scrambled siRNA (treated control), 100 nM taxol, transfection with a plasmid vector expressing Bcl-2 siRNA and taxol + Bcl-2 siRNA. (A) FACS dot plots of U251MG cells. Before FACS analysis, the cells were treated with 50 μg/ml propidium iodide for 30 min. at 4°C in dark. Population in the M1 area represents the apoptotic/dead cells. (B) FACS histograms of U251MG cells. The prominent increase in population of cells in the sub-G1 phase (M1) indicated increase in apoptosis after treatment with taxol or Bcl-2 siRNA or both. (C) Quantitative presentation of DNA fragmentation data from FACS analysis to indicate percent changes in live and apoptotic cells. Data are representative of four independent experiments (* P

    Article Snippet: Taxol (also known as paclitaxel, 6 mg/ml) was procured from Bristol-Myers Squibb (Princeton, NJ, USA) and diluted to a 1-mM solution in dimethylsulfoxide and protected from light.

    Techniques: FACS, Transfection, Plasmid Preparation, Expressing

    In situ stainings for biochemical markers of apoptosis in U251MG cells. Treatment (72 hrs) of cells: transfection with a plasmid vector expressing scrambled siRNA (treated control), 100 nM taxol, transfection with a plasmid vector expressing Bcl-2 siRNA and taxol + Bcl-2 siRNA. (A) Double immunofluorescent stainings to examine active fragments of caspase-9 and caspase-3. The cells were incubated overnight at 4°C with specific antibodies for active fragments of caspase-9 and caspase-3, washed and then treated with FITC conjugated and Texas red conjugated secondary antibodies at room temperature for 1 hr. Hoechst 33342 was used to counterstain the nucleus. Merged microphotographs demonstrated simultaneous expression of active fragments of caspase-9 and caspase-3 as well as disintegration of nucleus in the apoptotic cells (shown with arrows). (B) Fluorescent TUNEL assay for detection of apoptotic cells. Treatment with combination of taxol and Bcl-2 siRNA resulted in more apoptotic cell death than either treatment alone. (C) Quantitation of TUNEL-positive cells. Data are representative of four independent experiments (* P

    Journal: Journal of Cellular and Molecular Medicine

    Article Title: Combination of taxol and Bcl-2 siRNA induces apoptosis in human glioblastoma cells and inhibits invasion, angiogenesis and tumour growth

    doi: 10.1111/j.1582-4934.2008.00539.x

    Figure Lengend Snippet: In situ stainings for biochemical markers of apoptosis in U251MG cells. Treatment (72 hrs) of cells: transfection with a plasmid vector expressing scrambled siRNA (treated control), 100 nM taxol, transfection with a plasmid vector expressing Bcl-2 siRNA and taxol + Bcl-2 siRNA. (A) Double immunofluorescent stainings to examine active fragments of caspase-9 and caspase-3. The cells were incubated overnight at 4°C with specific antibodies for active fragments of caspase-9 and caspase-3, washed and then treated with FITC conjugated and Texas red conjugated secondary antibodies at room temperature for 1 hr. Hoechst 33342 was used to counterstain the nucleus. Merged microphotographs demonstrated simultaneous expression of active fragments of caspase-9 and caspase-3 as well as disintegration of nucleus in the apoptotic cells (shown with arrows). (B) Fluorescent TUNEL assay for detection of apoptotic cells. Treatment with combination of taxol and Bcl-2 siRNA resulted in more apoptotic cell death than either treatment alone. (C) Quantitation of TUNEL-positive cells. Data are representative of four independent experiments (* P

    Article Snippet: Taxol (also known as paclitaxel, 6 mg/ml) was procured from Bristol-Myers Squibb (Princeton, NJ, USA) and diluted to a 1-mM solution in dimethylsulfoxide and protected from light.

    Techniques: In Situ, Transfection, Plasmid Preparation, Expressing, Incubation, TUNEL Assay, Quantitation Assay

    In vivo angiogenesis (dorsal skinfold) assay. Treatment (72 hrs) of cells: transfection with a plasmid vector expressing scrambled siRNA (treated control), 100 nM taxol, transfection with a plasmid vector expressing Bcl-2 siRNA and taxol + Bcl-2 siRNA. The U251MG cells (2 × 10 5 ) from each treatment were suspended in 200 μl of serum-free medium and injected into a diffusion chamber. Then, diffusion chambers were surgically implanted under the dorsal skin of nude mice and left for 10 days. (A) In vivo angiogenesis in terms of development of neovasculature. Strong development of tumour-induced neovasculature (TN) with curved thin structures (as indicated by TN arrows) arising from pre-existing vasculature (PV) with relatively straight structures (as indicated by PV arrows) was observed in nude mice with U251MG cells untreated (not shown) and transfected with scrambled siRNA vector. The formation of such neovasculature was considerably reduced in nude mice with U251MG cells treated with taxol or Bcl-2 siRNA and completely inhibited in nude mice with U251MG cells treated with combination of taxol and Bcl-2 siRNA. (B) Quantitative presentation of neovasculature to indicate the extent of in vivo angiogenesis. The measurement of the TN was performed with the help of an ocular micrometer. Values are presented as mean ± S.D. of TN in six animals from each treatment group (* P

    Journal: Journal of Cellular and Molecular Medicine

    Article Title: Combination of taxol and Bcl-2 siRNA induces apoptosis in human glioblastoma cells and inhibits invasion, angiogenesis and tumour growth

    doi: 10.1111/j.1582-4934.2008.00539.x

    Figure Lengend Snippet: In vivo angiogenesis (dorsal skinfold) assay. Treatment (72 hrs) of cells: transfection with a plasmid vector expressing scrambled siRNA (treated control), 100 nM taxol, transfection with a plasmid vector expressing Bcl-2 siRNA and taxol + Bcl-2 siRNA. The U251MG cells (2 × 10 5 ) from each treatment were suspended in 200 μl of serum-free medium and injected into a diffusion chamber. Then, diffusion chambers were surgically implanted under the dorsal skin of nude mice and left for 10 days. (A) In vivo angiogenesis in terms of development of neovasculature. Strong development of tumour-induced neovasculature (TN) with curved thin structures (as indicated by TN arrows) arising from pre-existing vasculature (PV) with relatively straight structures (as indicated by PV arrows) was observed in nude mice with U251MG cells untreated (not shown) and transfected with scrambled siRNA vector. The formation of such neovasculature was considerably reduced in nude mice with U251MG cells treated with taxol or Bcl-2 siRNA and completely inhibited in nude mice with U251MG cells treated with combination of taxol and Bcl-2 siRNA. (B) Quantitative presentation of neovasculature to indicate the extent of in vivo angiogenesis. The measurement of the TN was performed with the help of an ocular micrometer. Values are presented as mean ± S.D. of TN in six animals from each treatment group (* P

    Article Snippet: Taxol (also known as paclitaxel, 6 mg/ml) was procured from Bristol-Myers Squibb (Princeton, NJ, USA) and diluted to a 1-mM solution in dimethylsulfoxide and protected from light.

    Techniques: In Vivo, Transfection, Plasmid Preparation, Expressing, Injection, Diffusion-based Assay, Mouse Assay

    Expression of Bcl-2 at mRNA and protein levels in U251MG cells. Treatment (72 hrs) of cells: control, 100 nM taxol, transfection with a plasmid vector carrying the scrambled siRNA cDNA, transfection with a plasmid vector carrying the Bcl-2 siRNA cDNA and taxol + Bcl-2 siRNA. In determination of both RNA and protein levels, GAPDH was used as an internal control. (A) Semi-quantitative RT-PCR for examination of Bcl-2 mRNA. (B) Western blotting for examination of Bcl-2 protein. (C) MTT assay for determination of percent changes in cell viability. For MTT assay, the cells were treated for 48 hrs. Data are representative of six independent experiments in duplicate (* P

    Journal: Journal of Cellular and Molecular Medicine

    Article Title: Combination of taxol and Bcl-2 siRNA induces apoptosis in human glioblastoma cells and inhibits invasion, angiogenesis and tumour growth

    doi: 10.1111/j.1582-4934.2008.00539.x

    Figure Lengend Snippet: Expression of Bcl-2 at mRNA and protein levels in U251MG cells. Treatment (72 hrs) of cells: control, 100 nM taxol, transfection with a plasmid vector carrying the scrambled siRNA cDNA, transfection with a plasmid vector carrying the Bcl-2 siRNA cDNA and taxol + Bcl-2 siRNA. In determination of both RNA and protein levels, GAPDH was used as an internal control. (A) Semi-quantitative RT-PCR for examination of Bcl-2 mRNA. (B) Western blotting for examination of Bcl-2 protein. (C) MTT assay for determination of percent changes in cell viability. For MTT assay, the cells were treated for 48 hrs. Data are representative of six independent experiments in duplicate (* P

    Article Snippet: Taxol (also known as paclitaxel, 6 mg/ml) was procured from Bristol-Myers Squibb (Princeton, NJ, USA) and diluted to a 1-mM solution in dimethylsulfoxide and protected from light.

    Techniques: Expressing, Transfection, Plasmid Preparation, Quantitative RT-PCR, Western Blot, MTT Assay

    Reduced cell proliferation and increased apoptosis in RG7787 plus nab-Paclitaxel-treated NCI-Meso29 tumors Mice were subcutaneously inoculated with 5x10 6 NCI-Meso29 cells and the treatment was started when tumors size reached 100 mm 3 . Mice were treated with no treatment; 1 cycle of 3x 2.5mg/kg RG7787 QOD i.v.; 1 cycle of 1 x 75 mg/kg nab-Paclitaxel and 1 cycle of 3 x 25mg/kg RG7787 combined with 1 cycle 1 x 75 mg/kg nab-Paclitaxel. Representative tumor tissues from different groups were harvested after the 1 st cycle of the indicated treatments on Day 33, and representative H E staining, IHC staining for MSLN and Ki-67 expression, as well as TUNEL staining with the paraffin sections of tumor tissues were shown. Scale bar in H E, 1000 μm. Scale bar in MSLN, Ki67, TUNEL staining, 200 μm.

    Journal: Clinical cancer research : an official journal of the American Association for Cancer Research

    Article Title: Efficacy of Anti-Mesothelin Immunotoxin RG7787 plus nab-Paclitaxel against Mesothelioma Patient Derived Xenografts and Mesothelin as a Biomarker of Tumor Response

    doi: 10.1158/1078-0432.CCR-16-1667

    Figure Lengend Snippet: Reduced cell proliferation and increased apoptosis in RG7787 plus nab-Paclitaxel-treated NCI-Meso29 tumors Mice were subcutaneously inoculated with 5x10 6 NCI-Meso29 cells and the treatment was started when tumors size reached 100 mm 3 . Mice were treated with no treatment; 1 cycle of 3x 2.5mg/kg RG7787 QOD i.v.; 1 cycle of 1 x 75 mg/kg nab-Paclitaxel and 1 cycle of 3 x 25mg/kg RG7787 combined with 1 cycle 1 x 75 mg/kg nab-Paclitaxel. Representative tumor tissues from different groups were harvested after the 1 st cycle of the indicated treatments on Day 33, and representative H E staining, IHC staining for MSLN and Ki-67 expression, as well as TUNEL staining with the paraffin sections of tumor tissues were shown. Scale bar in H E, 1000 μm. Scale bar in MSLN, Ki67, TUNEL staining, 200 μm.

    Article Snippet: For the in vitro combination study of RG7787 and nab-Paclitaxel, nab-Paclitaxel at a concentration of 10 ng/mL was added to the designated wells on day 1 after the cells were seeded and incubated overnight, then followed by adding different concentrations of RG7787 and incubated for 72 hours.

    Techniques: Mouse Assay, Staining, Immunohistochemistry, Expressing, TUNEL Assay

    In vitro cytotoxicity of RG7787 in combination with nab-Paclitaxel against primary mesothelioma cell lines, NCI-Meso16, NCI-Meso21 and NCI-Meso29 (A) Eight thousand tumor cells/well were seeded in a 96-well plate on day 0. Serial dilutions of nab-Paclitaxel were added on day 1 and serial dilutions of RG7787 were added on the following day either by itself or to wells treated the day before with Nab-Paclitaxel. After 4 days of incubation, cell viability was determined by WST-8. (B) To evaluate the effect of RG7787 plus nab-Paclitaxel on cell morphology 5x10 4 cells were seeded in a 24-well plate and 10 ng/ml of Nab-Paclitaxel was added, followed by the addition of 10 ng/ml of RG7787 the following day. The morphology of tumor cells after 4 days of incubation with nab-Paclitaxel alone, RG7787 alone or the two drugs together is shown as well as cell viability measured by WST-8.

    Journal: Clinical cancer research : an official journal of the American Association for Cancer Research

    Article Title: Efficacy of Anti-Mesothelin Immunotoxin RG7787 plus nab-Paclitaxel against Mesothelioma Patient Derived Xenografts and Mesothelin as a Biomarker of Tumor Response

    doi: 10.1158/1078-0432.CCR-16-1667

    Figure Lengend Snippet: In vitro cytotoxicity of RG7787 in combination with nab-Paclitaxel against primary mesothelioma cell lines, NCI-Meso16, NCI-Meso21 and NCI-Meso29 (A) Eight thousand tumor cells/well were seeded in a 96-well plate on day 0. Serial dilutions of nab-Paclitaxel were added on day 1 and serial dilutions of RG7787 were added on the following day either by itself or to wells treated the day before with Nab-Paclitaxel. After 4 days of incubation, cell viability was determined by WST-8. (B) To evaluate the effect of RG7787 plus nab-Paclitaxel on cell morphology 5x10 4 cells were seeded in a 24-well plate and 10 ng/ml of Nab-Paclitaxel was added, followed by the addition of 10 ng/ml of RG7787 the following day. The morphology of tumor cells after 4 days of incubation with nab-Paclitaxel alone, RG7787 alone or the two drugs together is shown as well as cell viability measured by WST-8.

    Article Snippet: For the in vitro combination study of RG7787 and nab-Paclitaxel, nab-Paclitaxel at a concentration of 10 ng/mL was added to the designated wells on day 1 after the cells were seeded and incubated overnight, then followed by adding different concentrations of RG7787 and incubated for 72 hours.

    Techniques: In Vitro, Incubation

    Evaluation of apoptosis induced by RG7787 and nab-Paclitaxel (A) Representative Annexin V-7-AAD apoptotic assay for NCI-Meso16 cell line either untreated or treated with nab-Paclitaxel, RG7787 or nab-Paclitaxel plus RG7787 combination. AnnexinV + 7AAD − cells are in early apoptotic stage while AnnexinV + 7AAD + cells are late apoptotic cells. (B) Percent of NCI-Meso16, NCI-Meso21 and NCI-Meso29 cells undergoing apoptosis after 72 h treatment with mono-therapy or combination. Out of the three cell lines tested, only in case of NCI-Meso16 the percent of apoptotic cells in the combination group was significantly higher than either of the single treatments.

    Journal: Clinical cancer research : an official journal of the American Association for Cancer Research

    Article Title: Efficacy of Anti-Mesothelin Immunotoxin RG7787 plus nab-Paclitaxel against Mesothelioma Patient Derived Xenografts and Mesothelin as a Biomarker of Tumor Response

    doi: 10.1158/1078-0432.CCR-16-1667

    Figure Lengend Snippet: Evaluation of apoptosis induced by RG7787 and nab-Paclitaxel (A) Representative Annexin V-7-AAD apoptotic assay for NCI-Meso16 cell line either untreated or treated with nab-Paclitaxel, RG7787 or nab-Paclitaxel plus RG7787 combination. AnnexinV + 7AAD − cells are in early apoptotic stage while AnnexinV + 7AAD + cells are late apoptotic cells. (B) Percent of NCI-Meso16, NCI-Meso21 and NCI-Meso29 cells undergoing apoptosis after 72 h treatment with mono-therapy or combination. Out of the three cell lines tested, only in case of NCI-Meso16 the percent of apoptotic cells in the combination group was significantly higher than either of the single treatments.

    Article Snippet: For the in vitro combination study of RG7787 and nab-Paclitaxel, nab-Paclitaxel at a concentration of 10 ng/mL was added to the designated wells on day 1 after the cells were seeded and incubated overnight, then followed by adding different concentrations of RG7787 and incubated for 72 hours.

    Techniques:

    In vivo efficacy of RG7787 plus nab-Paclitaxel against human mesothelioma tumor xenografts (A) NCI-Meso16 cells were grown as tumor xenografts in athymic nude mice. On day 44 when tumors reached 108 mm 3 groups of mice (n=8) were treated at time points indicated by vertical arrows with RG7787 (2.5 mg/kg), nab-Paclitaxel (100 mg/kg) or RG7787 (2.5 mg/kg) plus nab-Paclitaxel (100 mg/kg). Data points indicate mean tumor volumes and * shows comparison in mean tumor volume between mice treated with nab-Paclitaxel and RG7787 versus mice treated with nab-Paclitaxel alone. (B) NCI-Meso21 cells were also grown as tumor xenografts in athymic nude mice. On day 82 when tumors reached 102 mm 3 groups of mice (n=8) were treated at time points indicated by vertical arrows with RG7787 (2.5 mg/kg), nab-Paclitaxel (100 mg/kg) or RG7787 (2.5 mg/kg) plus nab-Paclitaxel (100 mg/kg). Data points indicate median tumor volumes and * shows comparison in median tumor volume between mice treated with nab-Paclitaxel and RG7787 versus mice treated with RG7787 alone. (C) NCI-Meso29 cells were grown as tumor xenografts in NOD-SCID mice and on day 25 when tumors were 102 mm 3 in size groups of mice (n=7) were treated at the time points indicated by vertical arrows with RG7787 (2.5 mg/kg), nab-Paclitaxel (75 mg/kg) or RG7787 (2.5 mg/kg) plus nab-Paclitaxel (75 mg/kg). Data points indicate median tumor volumes and * shows comparison in median tumor volume between mice treated with nab-Paclitaxel and RG7787 versus mice treated with nab-Paclitaxel alone.

    Journal: Clinical cancer research : an official journal of the American Association for Cancer Research

    Article Title: Efficacy of Anti-Mesothelin Immunotoxin RG7787 plus nab-Paclitaxel against Mesothelioma Patient Derived Xenografts and Mesothelin as a Biomarker of Tumor Response

    doi: 10.1158/1078-0432.CCR-16-1667

    Figure Lengend Snippet: In vivo efficacy of RG7787 plus nab-Paclitaxel against human mesothelioma tumor xenografts (A) NCI-Meso16 cells were grown as tumor xenografts in athymic nude mice. On day 44 when tumors reached 108 mm 3 groups of mice (n=8) were treated at time points indicated by vertical arrows with RG7787 (2.5 mg/kg), nab-Paclitaxel (100 mg/kg) or RG7787 (2.5 mg/kg) plus nab-Paclitaxel (100 mg/kg). Data points indicate mean tumor volumes and * shows comparison in mean tumor volume between mice treated with nab-Paclitaxel and RG7787 versus mice treated with nab-Paclitaxel alone. (B) NCI-Meso21 cells were also grown as tumor xenografts in athymic nude mice. On day 82 when tumors reached 102 mm 3 groups of mice (n=8) were treated at time points indicated by vertical arrows with RG7787 (2.5 mg/kg), nab-Paclitaxel (100 mg/kg) or RG7787 (2.5 mg/kg) plus nab-Paclitaxel (100 mg/kg). Data points indicate median tumor volumes and * shows comparison in median tumor volume between mice treated with nab-Paclitaxel and RG7787 versus mice treated with RG7787 alone. (C) NCI-Meso29 cells were grown as tumor xenografts in NOD-SCID mice and on day 25 when tumors were 102 mm 3 in size groups of mice (n=7) were treated at the time points indicated by vertical arrows with RG7787 (2.5 mg/kg), nab-Paclitaxel (75 mg/kg) or RG7787 (2.5 mg/kg) plus nab-Paclitaxel (75 mg/kg). Data points indicate median tumor volumes and * shows comparison in median tumor volume between mice treated with nab-Paclitaxel and RG7787 versus mice treated with nab-Paclitaxel alone.

    Article Snippet: For the in vitro combination study of RG7787 and nab-Paclitaxel, nab-Paclitaxel at a concentration of 10 ng/mL was added to the designated wells on day 1 after the cells were seeded and incubated overnight, then followed by adding different concentrations of RG7787 and incubated for 72 hours.

    Techniques: In Vivo, Mouse Assay

    Mesothelin expressions in early passage primary mesothelioma cells and cytotoxicity of RG7787 and nab-Paclitaxel (A) Primary mesothelioma cell cultures were stained with anti-mesothelin antibody MN followed by staining with goat anti-mouse antibody conjugated with R-PE and the binding was analyzed by flow cytometry. Results are shown in terms of histogram plots for each cell line where open area depicts the binding of MN antibody and the gray area shows the binding of the isotope control antibody. (B) Cytotoxicity of RG7787 against the primary mesothelioma cell cultures. Eight thousand tumor cells were seeded in a 96-well plate and serial dilutions of RG7787 were added. After 4 days of incubation, cell viability was measured by WST-8 assay. (C) Cytotoxicity of nab-Paclitaxel against primary mesothelioma cells. Eight thousand tumor cells were seeded in a 96-well plate and serial dilutions of Nab-Paclitaxel were added. The cells were incubated for 4 days and the percent of viable cells were determined by WST-8 assay. (D) Table summarizing mesothelin expression in the primary mesothelioma cell lines as well as their sensitivity to the immunotoxins SS1P and RG7787 as well as nab-Paclitaxel.

    Journal: Clinical cancer research : an official journal of the American Association for Cancer Research

    Article Title: Efficacy of Anti-Mesothelin Immunotoxin RG7787 plus nab-Paclitaxel against Mesothelioma Patient Derived Xenografts and Mesothelin as a Biomarker of Tumor Response

    doi: 10.1158/1078-0432.CCR-16-1667

    Figure Lengend Snippet: Mesothelin expressions in early passage primary mesothelioma cells and cytotoxicity of RG7787 and nab-Paclitaxel (A) Primary mesothelioma cell cultures were stained with anti-mesothelin antibody MN followed by staining with goat anti-mouse antibody conjugated with R-PE and the binding was analyzed by flow cytometry. Results are shown in terms of histogram plots for each cell line where open area depicts the binding of MN antibody and the gray area shows the binding of the isotope control antibody. (B) Cytotoxicity of RG7787 against the primary mesothelioma cell cultures. Eight thousand tumor cells were seeded in a 96-well plate and serial dilutions of RG7787 were added. After 4 days of incubation, cell viability was measured by WST-8 assay. (C) Cytotoxicity of nab-Paclitaxel against primary mesothelioma cells. Eight thousand tumor cells were seeded in a 96-well plate and serial dilutions of Nab-Paclitaxel were added. The cells were incubated for 4 days and the percent of viable cells were determined by WST-8 assay. (D) Table summarizing mesothelin expression in the primary mesothelioma cell lines as well as their sensitivity to the immunotoxins SS1P and RG7787 as well as nab-Paclitaxel.

    Article Snippet: For the in vitro combination study of RG7787 and nab-Paclitaxel, nab-Paclitaxel at a concentration of 10 ng/mL was added to the designated wells on day 1 after the cells were seeded and incubated overnight, then followed by adding different concentrations of RG7787 and incubated for 72 hours.

    Techniques: Staining, Binding Assay, Flow Cytometry, Cytometry, Incubation, Expressing

    Therapeutic classification of MMAE-conjugated nanoparticles using an shRNA screen. a Heat maps and RNAi signature classifications of conventional microtubule stabilizers (paclitaxel, docetaxel) and microtubule destabilizers (vincristine, vinblastine), the highly potent toxin MMAE, and its nanoparticle conjugate (NP(MMAE)). b Principal component analysis of RNAi signatures from each of these aforementioned agents as well as in relation to known transcription/translation inhibitors, topoisomerase II (topII) poisons, and the DNA cross-linkers reference sets

    Journal: Nature Communications

    Article Title: Nanoparticle conjugates of a highly potent toxin enhance safety and circumvent platinum resistance in ovarian cancer

    doi: 10.1038/s41467-017-02390-7

    Figure Lengend Snippet: Therapeutic classification of MMAE-conjugated nanoparticles using an shRNA screen. a Heat maps and RNAi signature classifications of conventional microtubule stabilizers (paclitaxel, docetaxel) and microtubule destabilizers (vincristine, vinblastine), the highly potent toxin MMAE, and its nanoparticle conjugate (NP(MMAE)). b Principal component analysis of RNAi signatures from each of these aforementioned agents as well as in relation to known transcription/translation inhibitors, topoisomerase II (topII) poisons, and the DNA cross-linkers reference sets

    Article Snippet: They have typically incorporated drugs with tolerable toxicity profiles such as doxorubicin (e.g., DOXIL® (doxorubicin HCl liposome injection); Johnson & Johnson) or paclitaxel (e.g., Abraxane® (paclitaxel protein-bound); Celgene), displaying modest activity against multiple cancer cell types (i.e., IC50 s in the tens to hundreds of nM range) , .

    Techniques: shRNA

    (A) Diagnostic angiography showed total occlusion of the paclitaxel eluting stent (arrow). (B) Final angiography after thrombus aspiration and balloon dilatation of the stent showed normal antegrade flow (TIMI 3).

    Journal: Heart

    Article Title: Late thrombotic occlusion of paclitaxel eluting stent more than one year after stent implantation

    doi: 10.1136/hrt.2004.033589

    Figure Lengend Snippet: (A) Diagnostic angiography showed total occlusion of the paclitaxel eluting stent (arrow). (B) Final angiography after thrombus aspiration and balloon dilatation of the stent showed normal antegrade flow (TIMI 3).

    Article Snippet: Emergency coronary angiography confirmed a totally occluded proximal LAD artery, the site of the paclitaxel eluting stent (panel A).

    Techniques: Diagnostic Assay, Flow Cytometry

    Effects of scheduled combinations of [DGln4]LR peptide with cDDP, paclitaxel, 5FU and RTX on the SQ values in 2008 and C13* cell lines. ( A ) concurrent combinations for 72 h. ( B ) Sequential combinations as described in Section 4 . The bars represent the mean of duplicate cell counts on three separate experiments and indicate the results of the inhibition of drug combinations divided by the sum of the inhibition of a single drug to obtain the values of SQ. Error bars, SD.

    Journal: International Journal of Molecular Sciences

    Article Title: A Peptidic Thymidylate-Synthase Inhibitor Loaded on Pegylated Liposomes Enhances the Antitumour Effect of Chemotherapy Drugs in Human Ovarian Cancer Cells

    doi: 10.3390/ijms21124452

    Figure Lengend Snippet: Effects of scheduled combinations of [DGln4]LR peptide with cDDP, paclitaxel, 5FU and RTX on the SQ values in 2008 and C13* cell lines. ( A ) concurrent combinations for 72 h. ( B ) Sequential combinations as described in Section 4 . The bars represent the mean of duplicate cell counts on three separate experiments and indicate the results of the inhibition of drug combinations divided by the sum of the inhibition of a single drug to obtain the values of SQ. Error bars, SD.

    Article Snippet: MaterialsRaltitrexed (RTX) and paclitaxel were purchased from Selleckchem (Houston, TX, USA) and were dissolved in DMSO immediately before addition to the cell cultures.

    Techniques: Inhibition

    Effects of scheduled combinations of [DGln4]LR peptide with cDDP, paclitaxel, 5FU and RTX on the SQ values in IGROV-1 cell line. (Left panel) Concurrent combinations for 72 hr. (Right panel) Sequential combinations as described in Section 4 . The bars represent the mean of duplicate cell counts on three separate experiments and indicate the results of the inhibition of drug combinations divided by the sum of the inhibition of a single drug to obtain the values of SQ. Error bars, SD.

    Journal: International Journal of Molecular Sciences

    Article Title: A Peptidic Thymidylate-Synthase Inhibitor Loaded on Pegylated Liposomes Enhances the Antitumour Effect of Chemotherapy Drugs in Human Ovarian Cancer Cells

    doi: 10.3390/ijms21124452

    Figure Lengend Snippet: Effects of scheduled combinations of [DGln4]LR peptide with cDDP, paclitaxel, 5FU and RTX on the SQ values in IGROV-1 cell line. (Left panel) Concurrent combinations for 72 hr. (Right panel) Sequential combinations as described in Section 4 . The bars represent the mean of duplicate cell counts on three separate experiments and indicate the results of the inhibition of drug combinations divided by the sum of the inhibition of a single drug to obtain the values of SQ. Error bars, SD.

    Article Snippet: MaterialsRaltitrexed (RTX) and paclitaxel were purchased from Selleckchem (Houston, TX, USA) and were dissolved in DMSO immediately before addition to the cell cultures.

    Techniques: Inhibition

    Effects of scheduled combinations of the [D-Gln4]LR peptide with cDDP, paclitaxel, 5FU and RTX on the SQ values in A2780 and A2780/CP cell lines. ( A ) concurrent combinations for 72 h. ( B ) Sequential combinations, as described in Section 4 . The bars represent the mean of duplicate cell counts on three separate experiments and indicate the result of the inhibition of drug combination divided by the sum of the inhibition of a single drug to obtain the values of SQ. Error bars, SD.

    Journal: International Journal of Molecular Sciences

    Article Title: A Peptidic Thymidylate-Synthase Inhibitor Loaded on Pegylated Liposomes Enhances the Antitumour Effect of Chemotherapy Drugs in Human Ovarian Cancer Cells

    doi: 10.3390/ijms21124452

    Figure Lengend Snippet: Effects of scheduled combinations of the [D-Gln4]LR peptide with cDDP, paclitaxel, 5FU and RTX on the SQ values in A2780 and A2780/CP cell lines. ( A ) concurrent combinations for 72 h. ( B ) Sequential combinations, as described in Section 4 . The bars represent the mean of duplicate cell counts on three separate experiments and indicate the result of the inhibition of drug combination divided by the sum of the inhibition of a single drug to obtain the values of SQ. Error bars, SD.

    Article Snippet: MaterialsRaltitrexed (RTX) and paclitaxel were purchased from Selleckchem (Houston, TX, USA) and were dissolved in DMSO immediately before addition to the cell cultures.

    Techniques: Inhibition

    Induction of polyploid multinucleated giant cancer cells through chemical inhibition of Aurora kinase signaling can serve as a strategy to identify anti-mitotic chemicals. a, Flow chart of the drug discovery project designed to identify probes selectively cytotoxic to NCI-H2122 cells. b, Proposed model for the anticipated outcome of screen identifying new anti-mitotic perturbagens. c, NCI-H2122 cells were treated with DMSO or 0.5 μM of MLN8237 and each of 12 chemical hits identified in a compound library screen. Cell viability was measured with a CellTiter-Glo assay. Paclitaxel was used as positive control. Structure of SW172170, the anti-mitotic candidate probe is shown. d, Cell lysates of NCI-H2122 cell line were collected 48-hours after treating with each chemical and immunoblotted to measure phosphorylated histone H3. ß-Actin was used as internal immunoblotting control. Normalized band intensities of phosphorylated Histone H3 from treated and untreated control samples are graphed. e, NCI-H2122 cells were treated with SW172170 for four days and visualized with bright-field or fluorescent microscopy. Hoechst reagent and monoclonal antibodies against Tubulin were used to visualize the nuclei and mitotic spindles, respectively (Scale bar, 25 μM).

    Journal: bioRxiv

    Article Title: Loss of Aurora kinase signaling allows lung cancer cells to adopt an alternative cell cycle and form multinucleated polyploid giant cells that resist anti-mitotic drugs

    doi: 10.1101/865337

    Figure Lengend Snippet: Induction of polyploid multinucleated giant cancer cells through chemical inhibition of Aurora kinase signaling can serve as a strategy to identify anti-mitotic chemicals. a, Flow chart of the drug discovery project designed to identify probes selectively cytotoxic to NCI-H2122 cells. b, Proposed model for the anticipated outcome of screen identifying new anti-mitotic perturbagens. c, NCI-H2122 cells were treated with DMSO or 0.5 μM of MLN8237 and each of 12 chemical hits identified in a compound library screen. Cell viability was measured with a CellTiter-Glo assay. Paclitaxel was used as positive control. Structure of SW172170, the anti-mitotic candidate probe is shown. d, Cell lysates of NCI-H2122 cell line were collected 48-hours after treating with each chemical and immunoblotted to measure phosphorylated histone H3. ß-Actin was used as internal immunoblotting control. Normalized band intensities of phosphorylated Histone H3 from treated and untreated control samples are graphed. e, NCI-H2122 cells were treated with SW172170 for four days and visualized with bright-field or fluorescent microscopy. Hoechst reagent and monoclonal antibodies against Tubulin were used to visualize the nuclei and mitotic spindles, respectively (Scale bar, 25 μM).

    Article Snippet: Reagents MLN8237 (Alisertib) (ChemieTek, CT-M8237), VX-689 (Selleckchem, S2770), AZD1152 (Barasertib) (Selleckchem, S1147), GSK1070916 (Selleckchem, S2740), VX-680 (Tozasertib) (Chemietek, CT-VX680), PHA-739358 (Danusertib) (Selleckchem, S1107), Paclitaxel (LC Labs, P-9600), Docetaxel (Sigma-Aldrich, 01885), Vinorelbine detartrate salt hydrate (Sigma-Aldrich, V2264), Vinblastine sulfate (Sigma-Aldrich, V1377), BI 6727 (Volasertib) (Selleckchem, S2235), GSK923295 (Selleckchem, S7090), Ispinesib (Cayman Chemical Company, 18014), VS-83 (Calbiochem, 178273), Gemcitabine (ChemieTek, CT-GEM), Carboplatin (Sigma-Aldrich, C2538), Cisplatin (Sigma-Aldrich, 232120), Etoposide (LC Labs, E-4488), Topotecan (Tocris, 4562), Doxorubucin hydrochloride (Sigma-Aldrich, D1515), Pemetrexed (Tocris, 6185), Methotrexate (Tocris, 1230), 5-Fluorouracil (Sigma-Aldrich, F6627), Aphidicollin (Calbiochem, 178273), Bafilomycin A (Sigma-Aldrich, B1793), Erlotinib (LC Labs, E-4497) was purchased in powder form and stored at 10 mM or 20 mM stock concentrations in dimethyl sulfoxide (DMSO) at −20 °C.

    Techniques: Inhibition, Glo Assay, Positive Control, Microscopy

    Pan-Aurora kinase inhibitors do not inhibit growth of NCI-H1693 cells. a, NCI-H1693 cells were treated with serial concentrations of VX-680 for four days and cell viability was measured with a CellTiter-Glo assay. b, NCI-H1693 cells were treated with serial concentrations of VX-680 for two days and apoptosis was measured with a CaspaseGlo 3/7 assay. c, d, Assays were repeated with PHA-739358 treatments. Data are means of triplicate biological replicates with s.d. Some error bars are smaller than the data symbols. e, NCI-H1693 cell line was treated with serial concentrations of VX-680 or f, PHA-739358 for seven days and cell growth was measured with a crystal violet staining assay. A concentration of MLN8237 specific for Aurora kinase A and an EC100 concentration of Paclitaxel were used as controls. g, h, Overlay of cell viability, caspase 3/7 activity and crystal violet staining images with immunoblotting results.

    Journal: bioRxiv

    Article Title: Loss of Aurora kinase signaling allows lung cancer cells to adopt an alternative cell cycle and form multinucleated polyploid giant cells that resist anti-mitotic drugs

    doi: 10.1101/865337

    Figure Lengend Snippet: Pan-Aurora kinase inhibitors do not inhibit growth of NCI-H1693 cells. a, NCI-H1693 cells were treated with serial concentrations of VX-680 for four days and cell viability was measured with a CellTiter-Glo assay. b, NCI-H1693 cells were treated with serial concentrations of VX-680 for two days and apoptosis was measured with a CaspaseGlo 3/7 assay. c, d, Assays were repeated with PHA-739358 treatments. Data are means of triplicate biological replicates with s.d. Some error bars are smaller than the data symbols. e, NCI-H1693 cell line was treated with serial concentrations of VX-680 or f, PHA-739358 for seven days and cell growth was measured with a crystal violet staining assay. A concentration of MLN8237 specific for Aurora kinase A and an EC100 concentration of Paclitaxel were used as controls. g, h, Overlay of cell viability, caspase 3/7 activity and crystal violet staining images with immunoblotting results.

    Article Snippet: Reagents MLN8237 (Alisertib) (ChemieTek, CT-M8237), VX-689 (Selleckchem, S2770), AZD1152 (Barasertib) (Selleckchem, S1147), GSK1070916 (Selleckchem, S2740), VX-680 (Tozasertib) (Chemietek, CT-VX680), PHA-739358 (Danusertib) (Selleckchem, S1107), Paclitaxel (LC Labs, P-9600), Docetaxel (Sigma-Aldrich, 01885), Vinorelbine detartrate salt hydrate (Sigma-Aldrich, V2264), Vinblastine sulfate (Sigma-Aldrich, V1377), BI 6727 (Volasertib) (Selleckchem, S2235), GSK923295 (Selleckchem, S7090), Ispinesib (Cayman Chemical Company, 18014), VS-83 (Calbiochem, 178273), Gemcitabine (ChemieTek, CT-GEM), Carboplatin (Sigma-Aldrich, C2538), Cisplatin (Sigma-Aldrich, 232120), Etoposide (LC Labs, E-4488), Topotecan (Tocris, 4562), Doxorubucin hydrochloride (Sigma-Aldrich, D1515), Pemetrexed (Tocris, 6185), Methotrexate (Tocris, 1230), 5-Fluorouracil (Sigma-Aldrich, F6627), Aphidicollin (Calbiochem, 178273), Bafilomycin A (Sigma-Aldrich, B1793), Erlotinib (LC Labs, E-4497) was purchased in powder form and stored at 10 mM or 20 mM stock concentrations in dimethyl sulfoxide (DMSO) at −20 °C.

    Techniques: Glo Assay, Staining, Concentration Assay, Activity Assay

    Aurora A inhibitors at higher concentrations antagonize their own cytotoxic activity and restore growth. a, NCI-H1693 cells were treated with serial concentrations of MLN8237 for four days and cell viability was measured with a CellTiter-Glo assay, which measures ATP. b, NCI-H1693 cell line was treated with serial concentrations of MLN8237 for two days and active apoptosis was measured with a CaspaseGlo 3/7 assay. c, d, CellTiter-Glo and CaspaseGlo 3/7 assays were repeated with VX-689 treatments. Data are means of triplicate biological replicates with s.d. Some error bars are smaller than the data symbols. e, NCI-H1693 cells were treated with serial concentrations of MLN8237 or g, VX-689 for seven days and cell growth quantified with a crystal violet staining assay. f, Cell lysates of NCI-H1693 cell line were collected 48-hours after treating with MLN8237 or h, VX-689 and immunoblotted to measure phosphorylated histone H3 and phosphorylated Aurora A, B, and C. Paclitaxel was used in both sets of immunoblots as positive control and B-Actin was used as internal immunoblotting control. i, j, Overlay of cell viability, caspase 3/7 activity and crystal violet staining images with immunoblotting results at Aurora A kinase selective and non-selective (pan-Aurora kinase) inhibitory concentrations of MLN8237 and VX-689.

    Journal: bioRxiv

    Article Title: Loss of Aurora kinase signaling allows lung cancer cells to adopt an alternative cell cycle and form multinucleated polyploid giant cells that resist anti-mitotic drugs

    doi: 10.1101/865337

    Figure Lengend Snippet: Aurora A inhibitors at higher concentrations antagonize their own cytotoxic activity and restore growth. a, NCI-H1693 cells were treated with serial concentrations of MLN8237 for four days and cell viability was measured with a CellTiter-Glo assay, which measures ATP. b, NCI-H1693 cell line was treated with serial concentrations of MLN8237 for two days and active apoptosis was measured with a CaspaseGlo 3/7 assay. c, d, CellTiter-Glo and CaspaseGlo 3/7 assays were repeated with VX-689 treatments. Data are means of triplicate biological replicates with s.d. Some error bars are smaller than the data symbols. e, NCI-H1693 cells were treated with serial concentrations of MLN8237 or g, VX-689 for seven days and cell growth quantified with a crystal violet staining assay. f, Cell lysates of NCI-H1693 cell line were collected 48-hours after treating with MLN8237 or h, VX-689 and immunoblotted to measure phosphorylated histone H3 and phosphorylated Aurora A, B, and C. Paclitaxel was used in both sets of immunoblots as positive control and B-Actin was used as internal immunoblotting control. i, j, Overlay of cell viability, caspase 3/7 activity and crystal violet staining images with immunoblotting results at Aurora A kinase selective and non-selective (pan-Aurora kinase) inhibitory concentrations of MLN8237 and VX-689.

    Article Snippet: Reagents MLN8237 (Alisertib) (ChemieTek, CT-M8237), VX-689 (Selleckchem, S2770), AZD1152 (Barasertib) (Selleckchem, S1147), GSK1070916 (Selleckchem, S2740), VX-680 (Tozasertib) (Chemietek, CT-VX680), PHA-739358 (Danusertib) (Selleckchem, S1107), Paclitaxel (LC Labs, P-9600), Docetaxel (Sigma-Aldrich, 01885), Vinorelbine detartrate salt hydrate (Sigma-Aldrich, V2264), Vinblastine sulfate (Sigma-Aldrich, V1377), BI 6727 (Volasertib) (Selleckchem, S2235), GSK923295 (Selleckchem, S7090), Ispinesib (Cayman Chemical Company, 18014), VS-83 (Calbiochem, 178273), Gemcitabine (ChemieTek, CT-GEM), Carboplatin (Sigma-Aldrich, C2538), Cisplatin (Sigma-Aldrich, 232120), Etoposide (LC Labs, E-4488), Topotecan (Tocris, 4562), Doxorubucin hydrochloride (Sigma-Aldrich, D1515), Pemetrexed (Tocris, 6185), Methotrexate (Tocris, 1230), 5-Fluorouracil (Sigma-Aldrich, F6627), Aphidicollin (Calbiochem, 178273), Bafilomycin A (Sigma-Aldrich, B1793), Erlotinib (LC Labs, E-4497) was purchased in powder form and stored at 10 mM or 20 mM stock concentrations in dimethyl sulfoxide (DMSO) at −20 °C.

    Techniques: Activity Assay, Glo Assay, Staining, Western Blot, Positive Control

    Inhibition of Aurora kinase signaling provides resistance to anti-mitotic toxins, but not interphase toxins. a, NCI-H1693 cells were co-treated with DMSO or 0.5 μM of MLN8237 and IC100 concentrations of interphase or mitotic perturbagens. b, Cell viability and growth were assessed with a CellTiter-Glo assay (after four days of treatment) or c, crystal violet staining assay (after seven days of treatment), respectively. d, NCI-H1693 cells were co-treated with DMSO or 0.5 μM of MLN8237 and serial concentrations of Paclitaxel or Docetaxel. Cell viability was measured with a CellTiter-Glo assay. e, NCI-H1693 cell line was treated with 0.1 μM of MLN8237 and 0.2 μM AZD1152 or 20 nM GSK1070916 for four days. Treatment media were replaced with drug-free media for 14 days. Colony formation was measured with a crystal violet staining assay. Data of CellTiter-Glo assay are means of triplicate biological replicates with s.d. Some error bars are smaller than the data symbols. f, Proposed model of the cellular life cycle in the presence and absence of Aurora kinase signaling.

    Journal: bioRxiv

    Article Title: Loss of Aurora kinase signaling allows lung cancer cells to adopt an alternative cell cycle and form multinucleated polyploid giant cells that resist anti-mitotic drugs

    doi: 10.1101/865337

    Figure Lengend Snippet: Inhibition of Aurora kinase signaling provides resistance to anti-mitotic toxins, but not interphase toxins. a, NCI-H1693 cells were co-treated with DMSO or 0.5 μM of MLN8237 and IC100 concentrations of interphase or mitotic perturbagens. b, Cell viability and growth were assessed with a CellTiter-Glo assay (after four days of treatment) or c, crystal violet staining assay (after seven days of treatment), respectively. d, NCI-H1693 cells were co-treated with DMSO or 0.5 μM of MLN8237 and serial concentrations of Paclitaxel or Docetaxel. Cell viability was measured with a CellTiter-Glo assay. e, NCI-H1693 cell line was treated with 0.1 μM of MLN8237 and 0.2 μM AZD1152 or 20 nM GSK1070916 for four days. Treatment media were replaced with drug-free media for 14 days. Colony formation was measured with a crystal violet staining assay. Data of CellTiter-Glo assay are means of triplicate biological replicates with s.d. Some error bars are smaller than the data symbols. f, Proposed model of the cellular life cycle in the presence and absence of Aurora kinase signaling.

    Article Snippet: Reagents MLN8237 (Alisertib) (ChemieTek, CT-M8237), VX-689 (Selleckchem, S2770), AZD1152 (Barasertib) (Selleckchem, S1147), GSK1070916 (Selleckchem, S2740), VX-680 (Tozasertib) (Chemietek, CT-VX680), PHA-739358 (Danusertib) (Selleckchem, S1107), Paclitaxel (LC Labs, P-9600), Docetaxel (Sigma-Aldrich, 01885), Vinorelbine detartrate salt hydrate (Sigma-Aldrich, V2264), Vinblastine sulfate (Sigma-Aldrich, V1377), BI 6727 (Volasertib) (Selleckchem, S2235), GSK923295 (Selleckchem, S7090), Ispinesib (Cayman Chemical Company, 18014), VS-83 (Calbiochem, 178273), Gemcitabine (ChemieTek, CT-GEM), Carboplatin (Sigma-Aldrich, C2538), Cisplatin (Sigma-Aldrich, 232120), Etoposide (LC Labs, E-4488), Topotecan (Tocris, 4562), Doxorubucin hydrochloride (Sigma-Aldrich, D1515), Pemetrexed (Tocris, 6185), Methotrexate (Tocris, 1230), 5-Fluorouracil (Sigma-Aldrich, F6627), Aphidicollin (Calbiochem, 178273), Bafilomycin A (Sigma-Aldrich, B1793), Erlotinib (LC Labs, E-4497) was purchased in powder form and stored at 10 mM or 20 mM stock concentrations in dimethyl sulfoxide (DMSO) at −20 °C.

    Techniques: Inhibition, Glo Assay, Staining

    Aurora B, C inhibitors exhibit a camelback drug response pattern similar to Aurora A inhibitors. a, Cell lysates of NCI-H1693 cells were collected 48-hours after treating with AZD1152 (Barasertib) or b, GSK1070916 and immunoblotted to monitor phosphorylated histone H3 and phosphorylated Aurora A, B, C levels. Paclitaxel was used in both sets of immunoblots as positive control and B-Actin was used as internal immunoblotting control. c, NCI-H1693 cells were treated with serial concentrations of AZD1152 for four days and cell viability was measured with a CellTiter-Glo assay. d, NCI-H1693 cells were treated with serial concentrations of AZD1152 for two days and cell death was measured with a CaspaseGlo 3/7 assay. e, f, Assays were repeated with GSK1070916 treatments. Data are means of triplicate biological replicates with s.d. Some error bars are smaller than the data symbols. g, NCI-H1693 cell line was treated with serial concentrations of AZD1152 or h, GSK1070916 for seven days and cell growth was measured with a crystal violet staining assay. i, j, Overlay of cell viability, caspase 3/7 activity and crystal violet staining images with immunoblotting results at selective and non-selective concentrations of AZD1152 and GSK1070916.

    Journal: bioRxiv

    Article Title: Loss of Aurora kinase signaling allows lung cancer cells to adopt an alternative cell cycle and form multinucleated polyploid giant cells that resist anti-mitotic drugs

    doi: 10.1101/865337

    Figure Lengend Snippet: Aurora B, C inhibitors exhibit a camelback drug response pattern similar to Aurora A inhibitors. a, Cell lysates of NCI-H1693 cells were collected 48-hours after treating with AZD1152 (Barasertib) or b, GSK1070916 and immunoblotted to monitor phosphorylated histone H3 and phosphorylated Aurora A, B, C levels. Paclitaxel was used in both sets of immunoblots as positive control and B-Actin was used as internal immunoblotting control. c, NCI-H1693 cells were treated with serial concentrations of AZD1152 for four days and cell viability was measured with a CellTiter-Glo assay. d, NCI-H1693 cells were treated with serial concentrations of AZD1152 for two days and cell death was measured with a CaspaseGlo 3/7 assay. e, f, Assays were repeated with GSK1070916 treatments. Data are means of triplicate biological replicates with s.d. Some error bars are smaller than the data symbols. g, NCI-H1693 cell line was treated with serial concentrations of AZD1152 or h, GSK1070916 for seven days and cell growth was measured with a crystal violet staining assay. i, j, Overlay of cell viability, caspase 3/7 activity and crystal violet staining images with immunoblotting results at selective and non-selective concentrations of AZD1152 and GSK1070916.

    Article Snippet: Reagents MLN8237 (Alisertib) (ChemieTek, CT-M8237), VX-689 (Selleckchem, S2770), AZD1152 (Barasertib) (Selleckchem, S1147), GSK1070916 (Selleckchem, S2740), VX-680 (Tozasertib) (Chemietek, CT-VX680), PHA-739358 (Danusertib) (Selleckchem, S1107), Paclitaxel (LC Labs, P-9600), Docetaxel (Sigma-Aldrich, 01885), Vinorelbine detartrate salt hydrate (Sigma-Aldrich, V2264), Vinblastine sulfate (Sigma-Aldrich, V1377), BI 6727 (Volasertib) (Selleckchem, S2235), GSK923295 (Selleckchem, S7090), Ispinesib (Cayman Chemical Company, 18014), VS-83 (Calbiochem, 178273), Gemcitabine (ChemieTek, CT-GEM), Carboplatin (Sigma-Aldrich, C2538), Cisplatin (Sigma-Aldrich, 232120), Etoposide (LC Labs, E-4488), Topotecan (Tocris, 4562), Doxorubucin hydrochloride (Sigma-Aldrich, D1515), Pemetrexed (Tocris, 6185), Methotrexate (Tocris, 1230), 5-Fluorouracil (Sigma-Aldrich, F6627), Aphidicollin (Calbiochem, 178273), Bafilomycin A (Sigma-Aldrich, B1793), Erlotinib (LC Labs, E-4497) was purchased in powder form and stored at 10 mM or 20 mM stock concentrations in dimethyl sulfoxide (DMSO) at −20 °C.

    Techniques: Western Blot, Positive Control, Glo Assay, Staining, Activity Assay

    Combining Aurora A and B, C inhibitors at concentrations selective for their primary targets prevents cytotoxicity and allows cell growth. a, Cell lysates of NCI-H1693 cells were collected 48-hours after treating with combinations of MLN8237 and AZD1152 or b, MLN8237 and GSK1070916 and immunoblotted to detect phosphorylated histone H3 and phosphorylated Aurora A, B, C. Paclitaxel was used in both sets of immunoblots as a positive control and β-Actin was used as an internal immunoblotting control. c, NCI-H1693 cells were treated with combinations of MLN8237 and AZD1152 at concentrations selective for their primary targets for four days and cell viability was measured with a CellTiter-Glo assay. d, NCI-H1693 cells were treated with combinations of MLN8237 and AZD1152 at their selective for two days and cell death was measured with a CaspaseGlo 3/7 assay. e, f, Identical assays were repeated with GSK1070916 treatments. g, NCI-H1693 cells were treated with combinations of Aurora A and B/C selective inhibitors for seven days and cell growth was measured with a crystal violet staining assay. h, NCI-H1693 cells were treated with serial concentrations of MLN8237 in combination with serial dilutions of AZD1152 for four days and cell viability was measured with a CellTiter-Glo assay. i, j, Identical assays were repeated with GSK1070916 treatments. Data from CellTiter-Glo and CaspaseGlo 3/7 assays are presented as means of triplicate biological replicates with s.d. Some error bars are smaller than the data symbols.

    Journal: bioRxiv

    Article Title: Loss of Aurora kinase signaling allows lung cancer cells to adopt an alternative cell cycle and form multinucleated polyploid giant cells that resist anti-mitotic drugs

    doi: 10.1101/865337

    Figure Lengend Snippet: Combining Aurora A and B, C inhibitors at concentrations selective for their primary targets prevents cytotoxicity and allows cell growth. a, Cell lysates of NCI-H1693 cells were collected 48-hours after treating with combinations of MLN8237 and AZD1152 or b, MLN8237 and GSK1070916 and immunoblotted to detect phosphorylated histone H3 and phosphorylated Aurora A, B, C. Paclitaxel was used in both sets of immunoblots as a positive control and β-Actin was used as an internal immunoblotting control. c, NCI-H1693 cells were treated with combinations of MLN8237 and AZD1152 at concentrations selective for their primary targets for four days and cell viability was measured with a CellTiter-Glo assay. d, NCI-H1693 cells were treated with combinations of MLN8237 and AZD1152 at their selective for two days and cell death was measured with a CaspaseGlo 3/7 assay. e, f, Identical assays were repeated with GSK1070916 treatments. g, NCI-H1693 cells were treated with combinations of Aurora A and B/C selective inhibitors for seven days and cell growth was measured with a crystal violet staining assay. h, NCI-H1693 cells were treated with serial concentrations of MLN8237 in combination with serial dilutions of AZD1152 for four days and cell viability was measured with a CellTiter-Glo assay. i, j, Identical assays were repeated with GSK1070916 treatments. Data from CellTiter-Glo and CaspaseGlo 3/7 assays are presented as means of triplicate biological replicates with s.d. Some error bars are smaller than the data symbols.

    Article Snippet: Reagents MLN8237 (Alisertib) (ChemieTek, CT-M8237), VX-689 (Selleckchem, S2770), AZD1152 (Barasertib) (Selleckchem, S1147), GSK1070916 (Selleckchem, S2740), VX-680 (Tozasertib) (Chemietek, CT-VX680), PHA-739358 (Danusertib) (Selleckchem, S1107), Paclitaxel (LC Labs, P-9600), Docetaxel (Sigma-Aldrich, 01885), Vinorelbine detartrate salt hydrate (Sigma-Aldrich, V2264), Vinblastine sulfate (Sigma-Aldrich, V1377), BI 6727 (Volasertib) (Selleckchem, S2235), GSK923295 (Selleckchem, S7090), Ispinesib (Cayman Chemical Company, 18014), VS-83 (Calbiochem, 178273), Gemcitabine (ChemieTek, CT-GEM), Carboplatin (Sigma-Aldrich, C2538), Cisplatin (Sigma-Aldrich, 232120), Etoposide (LC Labs, E-4488), Topotecan (Tocris, 4562), Doxorubucin hydrochloride (Sigma-Aldrich, D1515), Pemetrexed (Tocris, 6185), Methotrexate (Tocris, 1230), 5-Fluorouracil (Sigma-Aldrich, F6627), Aphidicollin (Calbiochem, 178273), Bafilomycin A (Sigma-Aldrich, B1793), Erlotinib (LC Labs, E-4497) was purchased in powder form and stored at 10 mM or 20 mM stock concentrations in dimethyl sulfoxide (DMSO) at −20 °C.

    Techniques: Western Blot, Positive Control, Glo Assay, Staining

    Interfering with microtubules prevents formation of dendritic extensions by fibroblasts inside or on top of relaxed collagen matrices. ( A ) Fibroblasts were incubated 4 h in medium containing 50 ng/ml PDGF and other additions as indicated after which samples were fixed and stained for microtubules (green) and actin (red). ( Top ) Cells incubated on collagen-coated coverslips spread in an elongated, flattened morphology. Nocodazole (Noc, 5 μM) or taxol (5 μM) inhibited cell polarization but not spreading; cytochalasin D (Cyto D, 10 μM) inhibited spreading. ( Middle and Bottom ) Cells incubated inside or on top of relaxed collagen matrices spread by formation of dendritic extensions with microtubule cores and actin-rich tips. Nocodazole, taxol, or cytochalasin D prevented formation of dendritic extensions. ( B ) The same as A except the medium contained LPA instead of PDGF and incubation times were adjusted to allow for reformation of dendritic extensions. ( Top ) Cells incubated on collagen-coated coverslips spread in an elongated, flattened morphology. Nocodazole (5 μM) decreased cell polarization but not spreading; cytochalasin D (10 μM) inhibited spreading. ( Middle and Bottom ) After 4–24 h, cells incubated inside or on top of relaxed collagen matrices form bipolar extensions. Nocodazole or cytochalasin D prevented formation of extensions. (Scale bar: 50 μm.)

    Journal: Proceedings of the National Academy of Sciences of the United States of America

    Article Title: Microtubule function in fibroblast spreading is modulated according to the tension state of cell-matrix interactions

    doi: 10.1073/pnas.0608030104

    Figure Lengend Snippet: Interfering with microtubules prevents formation of dendritic extensions by fibroblasts inside or on top of relaxed collagen matrices. ( A ) Fibroblasts were incubated 4 h in medium containing 50 ng/ml PDGF and other additions as indicated after which samples were fixed and stained for microtubules (green) and actin (red). ( Top ) Cells incubated on collagen-coated coverslips spread in an elongated, flattened morphology. Nocodazole (Noc, 5 μM) or taxol (5 μM) inhibited cell polarization but not spreading; cytochalasin D (Cyto D, 10 μM) inhibited spreading. ( Middle and Bottom ) Cells incubated inside or on top of relaxed collagen matrices spread by formation of dendritic extensions with microtubule cores and actin-rich tips. Nocodazole, taxol, or cytochalasin D prevented formation of dendritic extensions. ( B ) The same as A except the medium contained LPA instead of PDGF and incubation times were adjusted to allow for reformation of dendritic extensions. ( Top ) Cells incubated on collagen-coated coverslips spread in an elongated, flattened morphology. Nocodazole (5 μM) decreased cell polarization but not spreading; cytochalasin D (10 μM) inhibited spreading. ( Middle and Bottom ) After 4–24 h, cells incubated inside or on top of relaxed collagen matrices form bipolar extensions. Nocodazole or cytochalasin D prevented formation of extensions. (Scale bar: 50 μm.)

    Article Snippet: Experimental incubation medium was DMEM containing 5 mg/ml BSA (fatty acid free) with PDGF (Upstate Biotechnology, Lake Placid, NY), LPA (Sigma, St. Louis, MO), nocodazole (Sigma), cytochalasin D (Sigma), taxol (Cytoskeleton, Denver), and blebbistatin (Toronto Research Chemicals, Downsview, ON, Canada) added as indicated in the figure legends.

    Techniques: Incubation, Staining

    Masitinib increases the cellular accumulation of [ 3 H]-paclitaxel and decreases the cellular efflux of [ 3 H]-paclitaxel in HEK293/ABCC10 cells. A, the accumulation of [ 3 H]-paclitaxel was measured after the cells (HEK293/pcDNA3.1 and HEK293/ABCC10) were

    Journal: Molecular cancer therapeutics

    Article Title: Masitinib Antagonizes ATP-Binding Cassette Subfamily C Member 10-Mediated Paclitaxel Resistance: A Preclinical Study

    doi: 10.1158/1535-7163.MCT-13-0743

    Figure Lengend Snippet: Masitinib increases the cellular accumulation of [ 3 H]-paclitaxel and decreases the cellular efflux of [ 3 H]-paclitaxel in HEK293/ABCC10 cells. A, the accumulation of [ 3 H]-paclitaxel was measured after the cells (HEK293/pcDNA3.1 and HEK293/ABCC10) were

    Article Snippet: Paclitaxel, docetaxel, vincristine, vinblastine and cisplatin were purchased from Tocris Bioscience (Ellisville, MO).

    Techniques:

    Masitinib significantly enhances the sensitivity of HEK293/ABCC10 cells to paclitaxel

    Journal: Molecular cancer therapeutics

    Article Title: Masitinib Antagonizes ATP-Binding Cassette Subfamily C Member 10-Mediated Paclitaxel Resistance: A Preclinical Study

    doi: 10.1158/1535-7163.MCT-13-0743

    Figure Lengend Snippet: Masitinib significantly enhances the sensitivity of HEK293/ABCC10 cells to paclitaxel

    Article Snippet: Paclitaxel, docetaxel, vincristine, vinblastine and cisplatin were purchased from Tocris Bioscience (Ellisville, MO).

    Techniques:

    Masitinib increases the cellular accumulation of BODIPY-paclitaxel in HEK293/ABCC10 cells. The accumulation of BODIPY-paclitaxel alone or with masitinib was measured after the cells (HEK293/pcDNA3.1 and HEK293/ABCC10) were pre-incubated with or without

    Journal: Molecular cancer therapeutics

    Article Title: Masitinib Antagonizes ATP-Binding Cassette Subfamily C Member 10-Mediated Paclitaxel Resistance: A Preclinical Study

    doi: 10.1158/1535-7163.MCT-13-0743

    Figure Lengend Snippet: Masitinib increases the cellular accumulation of BODIPY-paclitaxel in HEK293/ABCC10 cells. The accumulation of BODIPY-paclitaxel alone or with masitinib was measured after the cells (HEK293/pcDNA3.1 and HEK293/ABCC10) were pre-incubated with or without

    Article Snippet: Paclitaxel, docetaxel, vincristine, vinblastine and cisplatin were purchased from Tocris Bioscience (Ellisville, MO).

    Techniques: Incubation

    The effect of masitinib on the growth of ABCC10-expressing tumors in nude athymic mice. A, images of excised HEK293/ABCC10 tumors implanted subcutaneously in athymic NCR nude mice (n = 8) that were treated with vehicle, paclitaxel, mastinib or combination

    Journal: Molecular cancer therapeutics

    Article Title: Masitinib Antagonizes ATP-Binding Cassette Subfamily C Member 10-Mediated Paclitaxel Resistance: A Preclinical Study

    doi: 10.1158/1535-7163.MCT-13-0743

    Figure Lengend Snippet: The effect of masitinib on the growth of ABCC10-expressing tumors in nude athymic mice. A, images of excised HEK293/ABCC10 tumors implanted subcutaneously in athymic NCR nude mice (n = 8) that were treated with vehicle, paclitaxel, mastinib or combination

    Article Snippet: Paclitaxel, docetaxel, vincristine, vinblastine and cisplatin were purchased from Tocris Bioscience (Ellisville, MO).

    Techniques: Expressing, Mouse Assay

    The effect of masitinib and paclitaxel co-administration on plasma, intratumoral, and lung paclitaxel concentrations in mice. A, plasma at 10, 30, 60, 120, 240 min following administration (n = 7), B, paclitaxel concentrations in HEK293/ABCC10 tumors

    Journal: Molecular cancer therapeutics

    Article Title: Masitinib Antagonizes ATP-Binding Cassette Subfamily C Member 10-Mediated Paclitaxel Resistance: A Preclinical Study

    doi: 10.1158/1535-7163.MCT-13-0743

    Figure Lengend Snippet: The effect of masitinib and paclitaxel co-administration on plasma, intratumoral, and lung paclitaxel concentrations in mice. A, plasma at 10, 30, 60, 120, 240 min following administration (n = 7), B, paclitaxel concentrations in HEK293/ABCC10 tumors

    Article Snippet: Paclitaxel, docetaxel, vincristine, vinblastine and cisplatin were purchased from Tocris Bioscience (Ellisville, MO).

    Techniques: Mouse Assay

    HVGGSSV-nab-paclitaxel targeted to irradiated tumors a , LLC tumors grown in both hind limbs were treated with 3 Gy (left hind limb) or 0 Gy (right hind limb). Near-infrared (NIR) images acquired 72 hrs post-injection of mice after intravenous injection of Alexa fluor 750 labeled HVGGSSV-nab-paclitaxel, SGVSGHV-nab-paclitaxel, and unconjugated nab-paclitaxel. All images normalized to the same scale. Radiance was measured for both irradiated (3 Gy) and untreated (0 Gy) tumors. b , Bar graph of radiance for all treatment groups. The color scale bar indicates radiance in units of photons/s/cm 2 /sr. Shown are the mean and SEM for five animals in each group. Unpaired Student’s t test (p

    Journal: Clinical cancer research : an official journal of the American Association for Cancer Research

    Article Title: Radiation-guided drug delivery to mouse models of lung cancer

    doi: 10.1158/1078-0432.CCR-10-0969

    Figure Lengend Snippet: HVGGSSV-nab-paclitaxel targeted to irradiated tumors a , LLC tumors grown in both hind limbs were treated with 3 Gy (left hind limb) or 0 Gy (right hind limb). Near-infrared (NIR) images acquired 72 hrs post-injection of mice after intravenous injection of Alexa fluor 750 labeled HVGGSSV-nab-paclitaxel, SGVSGHV-nab-paclitaxel, and unconjugated nab-paclitaxel. All images normalized to the same scale. Radiance was measured for both irradiated (3 Gy) and untreated (0 Gy) tumors. b , Bar graph of radiance for all treatment groups. The color scale bar indicates radiance in units of photons/s/cm 2 /sr. Shown are the mean and SEM for five animals in each group. Unpaired Student’s t test (p

    Article Snippet: A scrambled version of HVGGSSV peptide (CGGGKKKGGGSGVSGHVN) was used as a control and conjugated to nab-paclitaxel in the same manner.

    Techniques: Irradiation, Injection, Mouse Assay, Labeling

    Therapeutic efficacy of targeted HVGGSSV-nab-paclitaxel in LLC and H460 xenografts Tumor growth delay studies: a , LLC murine lung carcinoma bearing C57 mice or b , H460 bearing nude mice were treated with either 3 Gy or 0 Gy and injected i.v. 5 hrs later with either targeted HVGGSSV-nab-paclitaxel, nab-paclitaxel, SGVSGHV-nab-paclitaxel or saline. Arrows indicate daily irradiation with 3 Gy every other day. Shown are graphs of fold volume increase with mean and SEM from five animals in each group. HVGGSSV-nab-paclitaxel combined with irradiation resulted in significantly greater tumor growth delay compared to tumors treated with SGVSGHV-nab-paclitaxel and irradiation or nab-paclitaxel and irradiation (p

    Journal: Clinical cancer research : an official journal of the American Association for Cancer Research

    Article Title: Radiation-guided drug delivery to mouse models of lung cancer

    doi: 10.1158/1078-0432.CCR-10-0969

    Figure Lengend Snippet: Therapeutic efficacy of targeted HVGGSSV-nab-paclitaxel in LLC and H460 xenografts Tumor growth delay studies: a , LLC murine lung carcinoma bearing C57 mice or b , H460 bearing nude mice were treated with either 3 Gy or 0 Gy and injected i.v. 5 hrs later with either targeted HVGGSSV-nab-paclitaxel, nab-paclitaxel, SGVSGHV-nab-paclitaxel or saline. Arrows indicate daily irradiation with 3 Gy every other day. Shown are graphs of fold volume increase with mean and SEM from five animals in each group. HVGGSSV-nab-paclitaxel combined with irradiation resulted in significantly greater tumor growth delay compared to tumors treated with SGVSGHV-nab-paclitaxel and irradiation or nab-paclitaxel and irradiation (p

    Article Snippet: A scrambled version of HVGGSSV peptide (CGGGKKKGGGSGVSGHVN) was used as a control and conjugated to nab-paclitaxel in the same manner.

    Techniques: Mouse Assay, Injection, Irradiation

    Colocalization HVGGSSV-nab-paclitaxel with tumor vascular endothelium Cryosections of LLC tumors from each treatment group were stained for vascular marker von Willebrand factor (vWF) (green) 3 hrs after treatment with a , 3 Gy and b , 0 Gy. HVGGSSV-nab-paclitaxel, SGVSGHV-nab-paclitaxel, and nab-paclitaxel labled with Alexa fluor 594 (red) prior to injection.

    Journal: Clinical cancer research : an official journal of the American Association for Cancer Research

    Article Title: Radiation-guided drug delivery to mouse models of lung cancer

    doi: 10.1158/1078-0432.CCR-10-0969

    Figure Lengend Snippet: Colocalization HVGGSSV-nab-paclitaxel with tumor vascular endothelium Cryosections of LLC tumors from each treatment group were stained for vascular marker von Willebrand factor (vWF) (green) 3 hrs after treatment with a , 3 Gy and b , 0 Gy. HVGGSSV-nab-paclitaxel, SGVSGHV-nab-paclitaxel, and nab-paclitaxel labled with Alexa fluor 594 (red) prior to injection.

    Article Snippet: A scrambled version of HVGGSSV peptide (CGGGKKKGGGSGVSGHVN) was used as a control and conjugated to nab-paclitaxel in the same manner.

    Techniques: Staining, Marker, Injection

    Biodistribution of targeted HVGGSSV-nab-paclitaxel a , Biodistribution of paclitaxel in tumor and tissues in each treatment group compared to nab-paclitaxel. Shown are the mean and SEM from three animals in each group. b , Tumor/plasma concentration ratios at 72 hrs post-injection. Shown are the mean and SEM from three animals in each group. c , Shown are paraffin sections immunohistochemically stained for paclitaxel presence (brown), and counterstained with hematoxylin (blue). Nuclei stained brown were scored as positive and nuclei that stained blue were scored as negative. Scale bar, 50 μm.

    Journal: Clinical cancer research : an official journal of the American Association for Cancer Research

    Article Title: Radiation-guided drug delivery to mouse models of lung cancer

    doi: 10.1158/1078-0432.CCR-10-0969

    Figure Lengend Snippet: Biodistribution of targeted HVGGSSV-nab-paclitaxel a , Biodistribution of paclitaxel in tumor and tissues in each treatment group compared to nab-paclitaxel. Shown are the mean and SEM from three animals in each group. b , Tumor/plasma concentration ratios at 72 hrs post-injection. Shown are the mean and SEM from three animals in each group. c , Shown are paraffin sections immunohistochemically stained for paclitaxel presence (brown), and counterstained with hematoxylin (blue). Nuclei stained brown were scored as positive and nuclei that stained blue were scored as negative. Scale bar, 50 μm.

    Article Snippet: A scrambled version of HVGGSSV peptide (CGGGKKKGGGSGVSGHVN) was used as a control and conjugated to nab-paclitaxel in the same manner.

    Techniques: Concentration Assay, Injection, Staining

    Effects of carboplatin and paclitaxel on the survival of H460 cells irradiated with X-rays or carbon-ion beams. Survival curves of cells receiving X-ray ( A ) and carbon-ion beam ( B ) irradiation. Carboplatin and paclitaxel were used at each respective IC 50 (7.9 μM and 8.3 nM). Datapoints were fitted to the linear–quadratic model. The mean ± SD is shown.

    Journal: Journal of Radiation Research

    Article Title: Radiosensitizing effect of carboplatin and paclitaxel to carbon-ion beam irradiation in the non-small-cell lung cancer cell line H460

    doi: 10.1093/jrr/rru085

    Figure Lengend Snippet: Effects of carboplatin and paclitaxel on the survival of H460 cells irradiated with X-rays or carbon-ion beams. Survival curves of cells receiving X-ray ( A ) and carbon-ion beam ( B ) irradiation. Carboplatin and paclitaxel were used at each respective IC 50 (7.9 μM and 8.3 nM). Datapoints were fitted to the linear–quadratic model. The mean ± SD is shown.

    Article Snippet: Chemotherapeutic drugs Carboplatin and paclitaxel (Wako Pure Chemical Industries, Tokyo, Japan) were solubilized in dimethyl sulfoxide (DMSO) and prepared as stock solutions at 100 mM and 1 mM, respectively.

    Techniques: Irradiation

    Effects of carboplatin and paclitaxel on senescence induction in H460 cells irradiated with X-rays or carbon-ion beams. ( A ) Representative micrograph of cells negative (left panel) and positive (right panel) for SA-β-gal staining. Cells positive for SA-β-gal staining are shown in blue. Bars, 100 μm. ( B ) Percentages of SA-β-gal-positive cells. The mean ± SD is shown. A single asterisk indicates P

    Journal: Journal of Radiation Research

    Article Title: Radiosensitizing effect of carboplatin and paclitaxel to carbon-ion beam irradiation in the non-small-cell lung cancer cell line H460

    doi: 10.1093/jrr/rru085

    Figure Lengend Snippet: Effects of carboplatin and paclitaxel on senescence induction in H460 cells irradiated with X-rays or carbon-ion beams. ( A ) Representative micrograph of cells negative (left panel) and positive (right panel) for SA-β-gal staining. Cells positive for SA-β-gal staining are shown in blue. Bars, 100 μm. ( B ) Percentages of SA-β-gal-positive cells. The mean ± SD is shown. A single asterisk indicates P

    Article Snippet: Chemotherapeutic drugs Carboplatin and paclitaxel (Wako Pure Chemical Industries, Tokyo, Japan) were solubilized in dimethyl sulfoxide (DMSO) and prepared as stock solutions at 100 mM and 1 mM, respectively.

    Techniques: Irradiation, Staining

    Effects of carboplatin and paclitaxel on apoptosis induction in H460 cells irradiated with X-rays or carbon-ion beams. ( A ) Representative micrograph of cells negative (left panel) and positive (right panel) for terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. TUNEL and 4,6-diamino-2-phenylindole (DAPI) staining are shown by green and blue fluorescence, respectively. Bars, 100 μm. ( B ) Percentages of TUNEL-positive cells. The mean ± SD is shown. A single asterisk indicates P

    Journal: Journal of Radiation Research

    Article Title: Radiosensitizing effect of carboplatin and paclitaxel to carbon-ion beam irradiation in the non-small-cell lung cancer cell line H460

    doi: 10.1093/jrr/rru085

    Figure Lengend Snippet: Effects of carboplatin and paclitaxel on apoptosis induction in H460 cells irradiated with X-rays or carbon-ion beams. ( A ) Representative micrograph of cells negative (left panel) and positive (right panel) for terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. TUNEL and 4,6-diamino-2-phenylindole (DAPI) staining are shown by green and blue fluorescence, respectively. Bars, 100 μm. ( B ) Percentages of TUNEL-positive cells. The mean ± SD is shown. A single asterisk indicates P

    Article Snippet: Chemotherapeutic drugs Carboplatin and paclitaxel (Wako Pure Chemical Industries, Tokyo, Japan) were solubilized in dimethyl sulfoxide (DMSO) and prepared as stock solutions at 100 mM and 1 mM, respectively.

    Techniques: Irradiation, End Labeling, TUNEL Assay, Staining, Fluorescence

    Effects of carboplatin and paclitaxel on the inhibition of H460 cell proliferation by X-ray or carbon-ion beam irradiation. Cell proliferation was calculated as the ratio of the number of viable cells in a treated group to that in the untreated control group 3 days after irradiation. Viable cells were determined by negativity for Trypan blue. Carboplatin and paclitaxel were used at each respective IC 50 (7.9 μM and 8.3 nM). The mean ± SD is shown. A single asterisk indicates P

    Journal: Journal of Radiation Research

    Article Title: Radiosensitizing effect of carboplatin and paclitaxel to carbon-ion beam irradiation in the non-small-cell lung cancer cell line H460

    doi: 10.1093/jrr/rru085

    Figure Lengend Snippet: Effects of carboplatin and paclitaxel on the inhibition of H460 cell proliferation by X-ray or carbon-ion beam irradiation. Cell proliferation was calculated as the ratio of the number of viable cells in a treated group to that in the untreated control group 3 days after irradiation. Viable cells were determined by negativity for Trypan blue. Carboplatin and paclitaxel were used at each respective IC 50 (7.9 μM and 8.3 nM). The mean ± SD is shown. A single asterisk indicates P

    Article Snippet: Chemotherapeutic drugs Carboplatin and paclitaxel (Wako Pure Chemical Industries, Tokyo, Japan) were solubilized in dimethyl sulfoxide (DMSO) and prepared as stock solutions at 100 mM and 1 mM, respectively.

    Techniques: Inhibition, Irradiation

    Cytotoxicity of carboplatin and paclitaxel in H460 cells assessed by clonogenic survival assay. ( A ) Carboplatin. ( B ) Paclitaxel. The mean ± SD is shown.

    Journal: Journal of Radiation Research

    Article Title: Radiosensitizing effect of carboplatin and paclitaxel to carbon-ion beam irradiation in the non-small-cell lung cancer cell line H460

    doi: 10.1093/jrr/rru085

    Figure Lengend Snippet: Cytotoxicity of carboplatin and paclitaxel in H460 cells assessed by clonogenic survival assay. ( A ) Carboplatin. ( B ) Paclitaxel. The mean ± SD is shown.

    Article Snippet: Chemotherapeutic drugs Carboplatin and paclitaxel (Wako Pure Chemical Industries, Tokyo, Japan) were solubilized in dimethyl sulfoxide (DMSO) and prepared as stock solutions at 100 mM and 1 mM, respectively.

    Techniques: Clonogenic Cell Survival Assay

    Effect of carboplatin and paclitaxel on TOV112D spheroids. The reference IC 50 is based on drug responses in TOV112D monolayer cultures. (a) Merged CTG-PI confocal section (image layer #13) of spheroids subjected to carboplatin and paclitaxel at different

    Journal: Biomicrofluidics

    Article Title: Empirical chemosensitivity testing in a spheroid model of ovarian cancer using a microfluidics-based multiplex platform

    doi: 10.1063/1.4774309

    Figure Lengend Snippet: Effect of carboplatin and paclitaxel on TOV112D spheroids. The reference IC 50 is based on drug responses in TOV112D monolayer cultures. (a) Merged CTG-PI confocal section (image layer #13) of spheroids subjected to carboplatin and paclitaxel at different

    Article Snippet: For this study, we selected two common ovarian cancer specific drugs namely carboplatin (stock solution—2.25 mg/ml in 5% dextrose, Novopharm, QC, Canada) and paclitaxel (stock solution—0.18 mg/ml in 5% dextrose, Hospira, QC, Canada).

    Techniques: CTG Assay

    Distribution rate vs elimination rate of nanoparticle albumin-bound paclitaxel ( nab -PTX) ( A ) and Kolliphor EL-paclitaxel micelles (KoEL-PTX) ( B ) in clinically relevant concentration ranges in human. The vertical dash line represents maximal plasma paclitaxel concentrations predicted from previous population pharmacokinetic analysis of each formulation.

    Journal: Clinical Pharmacology : Advances and Applications

    Article Title: Species difference in paclitaxel disposition correlated with poor pharmacological efficacy translation from mice to humans

    doi: 10.2147/CPAA.S185449

    Figure Lengend Snippet: Distribution rate vs elimination rate of nanoparticle albumin-bound paclitaxel ( nab -PTX) ( A ) and Kolliphor EL-paclitaxel micelles (KoEL-PTX) ( B ) in clinically relevant concentration ranges in human. The vertical dash line represents maximal plasma paclitaxel concentrations predicted from previous population pharmacokinetic analysis of each formulation.

    Article Snippet: Interestingly, no statistically significant difference in efficacy was observed between the KoEL-paclitaxel and nab -paclitaxel treatment groups.

    Techniques: Concentration Assay

    Total paclitaxel plasma concentration–time profiles on a linear scale ( A ) and a semilog scale ( B ) for Kolliphor EL-paclitaxel micelles (KoEL-PTX) and nanoparticle albumin-bound paclitaxel ( nab -PTX) following IV administration of 10 mg/kg in mice.

    Journal: Clinical Pharmacology : Advances and Applications

    Article Title: Species difference in paclitaxel disposition correlated with poor pharmacological efficacy translation from mice to humans

    doi: 10.2147/CPAA.S185449

    Figure Lengend Snippet: Total paclitaxel plasma concentration–time profiles on a linear scale ( A ) and a semilog scale ( B ) for Kolliphor EL-paclitaxel micelles (KoEL-PTX) and nanoparticle albumin-bound paclitaxel ( nab -PTX) following IV administration of 10 mg/kg in mice.

    Article Snippet: Interestingly, no statistically significant difference in efficacy was observed between the KoEL-paclitaxel and nab -paclitaxel treatment groups.

    Techniques: Concentration Assay, Mouse Assay

    Paclitaxel and anthrax toxin have additive but not synergistic anti-tumor activities. Average tumor sizes (a) and body weights (b) of mice receiving vehicle (circles), paclitaxel only (squares), PA-U2/LF only (upward triangles), or the combination (downward

    Journal: Investigational new drugs

    Article Title: Tumor therapy with a urokinase plasminogen activator-activated anthrax lethal toxin alone and in combination with paclitaxel

    doi: 10.1007/s10637-012-9847-1

    Figure Lengend Snippet: Paclitaxel and anthrax toxin have additive but not synergistic anti-tumor activities. Average tumor sizes (a) and body weights (b) of mice receiving vehicle (circles), paclitaxel only (squares), PA-U2/LF only (upward triangles), or the combination (downward

    Article Snippet: Paclitaxel was purchased from Teva Pharmaceuticals (Washington, DC).

    Techniques: Mouse Assay

    B16-BL6 mouse melanoma cells are not sensitized to PA toxins by prior paclitaxel treatment. Cells were seeded in 96-well plates, allowed to grow overnight, and treated with paclitaxel at 0–7.5 ng/mL for 24 h before the addition varying concentrations

    Journal: Investigational new drugs

    Article Title: Tumor therapy with a urokinase plasminogen activator-activated anthrax lethal toxin alone and in combination with paclitaxel

    doi: 10.1007/s10637-012-9847-1

    Figure Lengend Snippet: B16-BL6 mouse melanoma cells are not sensitized to PA toxins by prior paclitaxel treatment. Cells were seeded in 96-well plates, allowed to grow overnight, and treated with paclitaxel at 0–7.5 ng/mL for 24 h before the addition varying concentrations

    Article Snippet: Paclitaxel was purchased from Teva Pharmaceuticals (Washington, DC).

    Techniques:

    The effects of sipholenone E, sipholenol L and siphonellinol D on the accumulation of [ 3 H]-paclitaxel in KB-3-1 and KB-C2 cells The accumulation of [ 3 H]-paclitaxel was measured after preincubation with or without the reversal agents (10 μM) for 1 h at 37°C and then incubation with 0.1 μM [ 3 H]-paclitaxel in the presence or absence of the reversal agents for 2 h at 37°C. Afterwards, the cells were collected and the intracellular levels of [ 3 H]-paclitaxel were determined by scintillation counting. Verapamil was used as a positive control. Data points represent the means ± SD of triplicate determinations. Experiments were performed at least three independent times. * P

    Journal: Biochemical pharmacology

    Article Title: Marine sponge-derived sipholane triterpenoids reverse P-glycoprotein (ABCB1)-mediated multidrug resistance in cancer cells

    doi: 10.1016/j.bcp.2010.08.001

    Figure Lengend Snippet: The effects of sipholenone E, sipholenol L and siphonellinol D on the accumulation of [ 3 H]-paclitaxel in KB-3-1 and KB-C2 cells The accumulation of [ 3 H]-paclitaxel was measured after preincubation with or without the reversal agents (10 μM) for 1 h at 37°C and then incubation with 0.1 μM [ 3 H]-paclitaxel in the presence or absence of the reversal agents for 2 h at 37°C. Afterwards, the cells were collected and the intracellular levels of [ 3 H]-paclitaxel were determined by scintillation counting. Verapamil was used as a positive control. Data points represent the means ± SD of triplicate determinations. Experiments were performed at least three independent times. * P

    Article Snippet: [3 H]-paclitaxel (37.9 Ci/mmol) was purchased from Moravek Biochemicals Inc (Brea, CA, USA).

    Techniques: Incubation, Positive Control

    The effects of sipholenone E, sipholenol L and siphonellinol D on the efflux of [ 3 H]-paclitaxel from KB-3-1 and KB-C2 cells Cells were pre-treated with or without sipholenone E (A), sipholenol L (B) and siphonellinol D (C) at 10 μM for 1 h at 37°C and further incubated with 0.1 μM [ 3 H]-paclitaxel at 37°C for 2 h. Cells were then incubated in the fresh medium with or without the reversal agents for different time periods at 37°C. Cells were then collected and the intracellular levels of [ 3 H]-paclitaxel were determined by scintillation counting. A time course versus percentage of intracellular [ 3 H]-paclitaxel was plotted (0, 30, 60, 120 min). Verapamil (10 μM) was used as a positive control. Data points represent the means ± SD of triplicate determinations. Experiments were performed at least three independent times.

    Journal: Biochemical pharmacology

    Article Title: Marine sponge-derived sipholane triterpenoids reverse P-glycoprotein (ABCB1)-mediated multidrug resistance in cancer cells

    doi: 10.1016/j.bcp.2010.08.001

    Figure Lengend Snippet: The effects of sipholenone E, sipholenol L and siphonellinol D on the efflux of [ 3 H]-paclitaxel from KB-3-1 and KB-C2 cells Cells were pre-treated with or without sipholenone E (A), sipholenol L (B) and siphonellinol D (C) at 10 μM for 1 h at 37°C and further incubated with 0.1 μM [ 3 H]-paclitaxel at 37°C for 2 h. Cells were then incubated in the fresh medium with or without the reversal agents for different time periods at 37°C. Cells were then collected and the intracellular levels of [ 3 H]-paclitaxel were determined by scintillation counting. A time course versus percentage of intracellular [ 3 H]-paclitaxel was plotted (0, 30, 60, 120 min). Verapamil (10 μM) was used as a positive control. Data points represent the means ± SD of triplicate determinations. Experiments were performed at least three independent times.

    Article Snippet: [3 H]-paclitaxel (37.9 Ci/mmol) was purchased from Moravek Biochemicals Inc (Brea, CA, USA).

    Techniques: Incubation, Positive Control

    Tubulin polymerization is impaired in p35-expressing NPC-derived neural progeny following chemical microtubule disruption . For chemical disruption of microtubules, cultures were treated with 5 μg/mL nocodazole (Noc) for 3 hr, followed by washout and incubation in fresh differentiation media for 20 mins. NPC-derived neural progeny were fixed with glutaraldehyde and processed for β-tubulin immunofluorescence. (A,B) Chemically-induced disruption of microtubule structure in nocodazole-treated control NPC-derived neural progeny ( A ) was recovered by 20 mins post-washout ( B ). (C,D) Disruption of microtubule structure in nocodazole-treated p35-expressing NPC-derived neural progeny ( C ) appeared unchanged by 20 mins post-washout ( D ). (E) Quantitative image analysis of neurite outgrowth in NPC-derived neural progeny following treatment with nocodazole. Untreated control is shown for comparison to baseline neurite lengths. * p

    Journal: Molecular Neurodegeneration

    Article Title: Phosphorylation of collapsin response mediator protein-2 disrupts neuronal maturation in a model of adult neurogenesis: Implications for neurodegenerative disorders

    doi: 10.1186/1750-1326-6-67

    Figure Lengend Snippet: Tubulin polymerization is impaired in p35-expressing NPC-derived neural progeny following chemical microtubule disruption . For chemical disruption of microtubules, cultures were treated with 5 μg/mL nocodazole (Noc) for 3 hr, followed by washout and incubation in fresh differentiation media for 20 mins. NPC-derived neural progeny were fixed with glutaraldehyde and processed for β-tubulin immunofluorescence. (A,B) Chemically-induced disruption of microtubule structure in nocodazole-treated control NPC-derived neural progeny ( A ) was recovered by 20 mins post-washout ( B ). (C,D) Disruption of microtubule structure in nocodazole-treated p35-expressing NPC-derived neural progeny ( C ) appeared unchanged by 20 mins post-washout ( D ). (E) Quantitative image analysis of neurite outgrowth in NPC-derived neural progeny following treatment with nocodazole. Untreated control is shown for comparison to baseline neurite lengths. * p

    Article Snippet: Live-cell staining and imaging of polymerized tubulin in NPC-derived neural progeny For staining of polymerized tubulin in live cells, NPC-derived neural progeny treated with vehicle control or p35-adv were grown on glass coverslips in 12-well plates as described above, and incubated with Tubulin Tracker Green (Invitrogen) according to the manufacturer's guidelines.

    Techniques: Expressing, Derivative Assay, Incubation, Immunofluorescence

    Expression of S522A-CRMP2 mutant construct rescues neurite deficits in p35-expressing NPC-derived neural progeny . Differentiating NPCs were transfected on day 2 with wild-type (WT) human CRMP2 or mutated S522A-CRMP2 plasmids, followed by infection with p35 adenovirus. Cells were fixed on day 4 of differentiation with glutaraldehyde for β-tubulin immunofluorescence, or lysed for immunoblot analysis. (A-F) Immunocytochemical analysis of β-tubulin immunoreactivity showed reduced β-tubulin-positive neurites in NPC-derived neural progeny infected with p35-adv with or without co-expression of WT-CRMP2, and rescue with co-expression of S522A-CRMP2 plasmid. (G) Image analysis showing reduced β-tubulin-positive neurite lengths in p35-expressing and p35+WT-CRMP2 NPC-derived neural progeny that was recovered after co-expression of p35 and S522A-CRMP2. (H) Immunoblot analysis showing levels of CRMP2 phosphorylation in p35-expressing NPC-derived neural progeny transfected with S522A-CRMP2 or WT-CRMP2 plasmid. (I) Semi-quantitative image analysis of ratios of pSer522-CRMP2 (pCRMP2)/total CRMP2 (tCRMP2) levels in NPC-derived neural progeny expressing p35 with and without WT-CRMP2 or S522A-CRMP2 co-expression. * p

    Journal: Molecular Neurodegeneration

    Article Title: Phosphorylation of collapsin response mediator protein-2 disrupts neuronal maturation in a model of adult neurogenesis: Implications for neurodegenerative disorders

    doi: 10.1186/1750-1326-6-67

    Figure Lengend Snippet: Expression of S522A-CRMP2 mutant construct rescues neurite deficits in p35-expressing NPC-derived neural progeny . Differentiating NPCs were transfected on day 2 with wild-type (WT) human CRMP2 or mutated S522A-CRMP2 plasmids, followed by infection with p35 adenovirus. Cells were fixed on day 4 of differentiation with glutaraldehyde for β-tubulin immunofluorescence, or lysed for immunoblot analysis. (A-F) Immunocytochemical analysis of β-tubulin immunoreactivity showed reduced β-tubulin-positive neurites in NPC-derived neural progeny infected with p35-adv with or without co-expression of WT-CRMP2, and rescue with co-expression of S522A-CRMP2 plasmid. (G) Image analysis showing reduced β-tubulin-positive neurite lengths in p35-expressing and p35+WT-CRMP2 NPC-derived neural progeny that was recovered after co-expression of p35 and S522A-CRMP2. (H) Immunoblot analysis showing levels of CRMP2 phosphorylation in p35-expressing NPC-derived neural progeny transfected with S522A-CRMP2 or WT-CRMP2 plasmid. (I) Semi-quantitative image analysis of ratios of pSer522-CRMP2 (pCRMP2)/total CRMP2 (tCRMP2) levels in NPC-derived neural progeny expressing p35 with and without WT-CRMP2 or S522A-CRMP2 co-expression. * p

    Article Snippet: Live-cell staining and imaging of polymerized tubulin in NPC-derived neural progeny For staining of polymerized tubulin in live cells, NPC-derived neural progeny treated with vehicle control or p35-adv were grown on glass coverslips in 12-well plates as described above, and incubated with Tubulin Tracker Green (Invitrogen) according to the manufacturer's guidelines.

    Techniques: Expressing, Mutagenesis, Construct, Derivative Assay, Transfection, Infection, Immunofluorescence, Plasmid Preparation

    Live-cell imaging of polymerized tubulin distribution, and ultrastructural analysis of microtubules in NPC-derived neural progeny with CDK5 activation . Differentiating NPCs were infected on day 2 with an adenoviral vector expressing p35. For live imaging of tubulin distribution, on day 4, cells on coverslips were incubated with Tubulin Tracker Green to stain polymerized tubulin. Coverslips were imaged using a fluorescent microscope. For electron microscopy analysis, NPCs were grown on coverslips embedded in 35 mm dishes, fixed in glutaraldehyde and processed for electron microscopic analysis. (A,B) Live-cell imaging of polymerized tubulin stained with Tubulin Tracker in cell bodies and processes of NPC-derived neural progeny infected with p35-adv. (A) Under control conditions, polymerized tubulin is apparent in bundled microtubule structures in cell processes (arrows). (B) Under conditions of abnormal CDK5 activation, polymerized tubulin staining was primarily detected in diffuse, cytoplasmic fibers (arrows). (C,D) Electron microscopy images showing organized cytoskeletal structure in control NPC-derived neural progeny with long, parallel tubule structures (arrows) along the processes of cells. (E,F) NPC-derived neural progeny expressing high levels of p35 displayed a disorganized cytoskeleton with less abundant, short and web-like filamentous structures (arrows) in the processes of cells. Scale bar = 30 μm (A,B); 0.5 μm (C,E); 0.25 μm (D,F).

    Journal: Molecular Neurodegeneration

    Article Title: Phosphorylation of collapsin response mediator protein-2 disrupts neuronal maturation in a model of adult neurogenesis: Implications for neurodegenerative disorders

    doi: 10.1186/1750-1326-6-67

    Figure Lengend Snippet: Live-cell imaging of polymerized tubulin distribution, and ultrastructural analysis of microtubules in NPC-derived neural progeny with CDK5 activation . Differentiating NPCs were infected on day 2 with an adenoviral vector expressing p35. For live imaging of tubulin distribution, on day 4, cells on coverslips were incubated with Tubulin Tracker Green to stain polymerized tubulin. Coverslips were imaged using a fluorescent microscope. For electron microscopy analysis, NPCs were grown on coverslips embedded in 35 mm dishes, fixed in glutaraldehyde and processed for electron microscopic analysis. (A,B) Live-cell imaging of polymerized tubulin stained with Tubulin Tracker in cell bodies and processes of NPC-derived neural progeny infected with p35-adv. (A) Under control conditions, polymerized tubulin is apparent in bundled microtubule structures in cell processes (arrows). (B) Under conditions of abnormal CDK5 activation, polymerized tubulin staining was primarily detected in diffuse, cytoplasmic fibers (arrows). (C,D) Electron microscopy images showing organized cytoskeletal structure in control NPC-derived neural progeny with long, parallel tubule structures (arrows) along the processes of cells. (E,F) NPC-derived neural progeny expressing high levels of p35 displayed a disorganized cytoskeleton with less abundant, short and web-like filamentous structures (arrows) in the processes of cells. Scale bar = 30 μm (A,B); 0.5 μm (C,E); 0.25 μm (D,F).

    Article Snippet: Live-cell staining and imaging of polymerized tubulin in NPC-derived neural progeny For staining of polymerized tubulin in live cells, NPC-derived neural progeny treated with vehicle control or p35-adv were grown on glass coverslips in 12-well plates as described above, and incubated with Tubulin Tracker Green (Invitrogen) according to the manufacturer's guidelines.

    Techniques: Live Cell Imaging, Derivative Assay, Activation Assay, Infection, Plasmid Preparation, Expressing, Imaging, Incubation, Staining, Microscopy, Electron Microscopy

    Increased CRMP2 phosphorylation in NPCs treated with HIV-gp120 protein, and rescue with CDK5 siRNA knockdown . Differentiating NPCs were transfected day 2 of differentiation with siRNA specific for CDK5 (siCDK5) or transfection reagent control, followed by treatment with recombinant HIV-gp120 protein (100 ng/mL) or vehicle control. Cells were fixed on day 4 of differentiation for double-immunolabeling analysis with antibodies against β-III Tubulin (immature neuronal marker) and pSer522-CRMP2 (pSer-CRMP2). (A-C) β-III Tubulin-positive NPC-derived neuronal progeny treated with vehicle control express background levels of pSer-CRMP2. (D-F) NPC-derived neuronal progeny treated with gp120 for 48 hrs display increased pSer-CRMP2 immunoreactivity in β-III Tubulin-positive cells. (G-I) β-III Tubulin-positive NPC-derived neuronal progeny treated with siCDK5 show low levels of pSer-CRMP2 immunoreactivity. (J-L) β-III Tubulin-positive NPC-derived neuronal progeny treated with siCDK5 and gp120 show background levels of pSer-CRMP2 immunoreactivity. (M, N) Semi-quantitative image analysis of β-III Tubulin (M) and pSer-CRMP2 (N) immunoreactivity. * p

    Journal: Molecular Neurodegeneration

    Article Title: Phosphorylation of collapsin response mediator protein-2 disrupts neuronal maturation in a model of adult neurogenesis: Implications for neurodegenerative disorders

    doi: 10.1186/1750-1326-6-67

    Figure Lengend Snippet: Increased CRMP2 phosphorylation in NPCs treated with HIV-gp120 protein, and rescue with CDK5 siRNA knockdown . Differentiating NPCs were transfected day 2 of differentiation with siRNA specific for CDK5 (siCDK5) or transfection reagent control, followed by treatment with recombinant HIV-gp120 protein (100 ng/mL) or vehicle control. Cells were fixed on day 4 of differentiation for double-immunolabeling analysis with antibodies against β-III Tubulin (immature neuronal marker) and pSer522-CRMP2 (pSer-CRMP2). (A-C) β-III Tubulin-positive NPC-derived neuronal progeny treated with vehicle control express background levels of pSer-CRMP2. (D-F) NPC-derived neuronal progeny treated with gp120 for 48 hrs display increased pSer-CRMP2 immunoreactivity in β-III Tubulin-positive cells. (G-I) β-III Tubulin-positive NPC-derived neuronal progeny treated with siCDK5 show low levels of pSer-CRMP2 immunoreactivity. (J-L) β-III Tubulin-positive NPC-derived neuronal progeny treated with siCDK5 and gp120 show background levels of pSer-CRMP2 immunoreactivity. (M, N) Semi-quantitative image analysis of β-III Tubulin (M) and pSer-CRMP2 (N) immunoreactivity. * p

    Article Snippet: Live-cell staining and imaging of polymerized tubulin in NPC-derived neural progeny For staining of polymerized tubulin in live cells, NPC-derived neural progeny treated with vehicle control or p35-adv were grown on glass coverslips in 12-well plates as described above, and incubated with Tubulin Tracker Green (Invitrogen) according to the manufacturer's guidelines.

    Techniques: Transfection, Recombinant, Immunolabeling, Marker, Derivative Assay

    Impaired neurite outgrowth is accompanied by CRMP2 hyperphosphorylation in NPC-derived neural progeny overexpressing p35 . Differentiating NPCs were grown on glass coverslips and infected on day 2 with an adenoviral vector expressing p35. Cells were processed for immunocytochemistry and immunoblot analyses. For β-tubulin immunofluorescence, on day 4, cells were briefly extracted, then fixed with glutaraldehyde and processed. (A,B) Reduced β-tubulin-immunoreactive neurites in NPC-derived neural progeny infected with p35-adv. (C) Quantitative image analysis showing reduced neurite lengths in NPC-derived neural progeny with p35 expression. (D) Immunoblot analysis of cell lysates from control and p35-expressing NPCs using a panel of antibodies specific for various isoforms and phosphorylated forms of CRMP. (E) Immunoblot analysis of total cell lysates showing increased CRMP2 phosphorylation in NPC-derived neural progeny expressing p35 from adenoviral (left panel) or plasmid (right panel) vectors. (F) Semi-quantitative image analysis of fold change in CRMP2 phosphorylation at the CDK5 epitope (Ser522) in immunoblots from cells expressing p35 from adenoviral or plasmid vectors. * p

    Journal: Molecular Neurodegeneration

    Article Title: Phosphorylation of collapsin response mediator protein-2 disrupts neuronal maturation in a model of adult neurogenesis: Implications for neurodegenerative disorders

    doi: 10.1186/1750-1326-6-67

    Figure Lengend Snippet: Impaired neurite outgrowth is accompanied by CRMP2 hyperphosphorylation in NPC-derived neural progeny overexpressing p35 . Differentiating NPCs were grown on glass coverslips and infected on day 2 with an adenoviral vector expressing p35. Cells were processed for immunocytochemistry and immunoblot analyses. For β-tubulin immunofluorescence, on day 4, cells were briefly extracted, then fixed with glutaraldehyde and processed. (A,B) Reduced β-tubulin-immunoreactive neurites in NPC-derived neural progeny infected with p35-adv. (C) Quantitative image analysis showing reduced neurite lengths in NPC-derived neural progeny with p35 expression. (D) Immunoblot analysis of cell lysates from control and p35-expressing NPCs using a panel of antibodies specific for various isoforms and phosphorylated forms of CRMP. (E) Immunoblot analysis of total cell lysates showing increased CRMP2 phosphorylation in NPC-derived neural progeny expressing p35 from adenoviral (left panel) or plasmid (right panel) vectors. (F) Semi-quantitative image analysis of fold change in CRMP2 phosphorylation at the CDK5 epitope (Ser522) in immunoblots from cells expressing p35 from adenoviral or plasmid vectors. * p

    Article Snippet: Live-cell staining and imaging of polymerized tubulin in NPC-derived neural progeny For staining of polymerized tubulin in live cells, NPC-derived neural progeny treated with vehicle control or p35-adv were grown on glass coverslips in 12-well plates as described above, and incubated with Tubulin Tracker Green (Invitrogen) according to the manufacturer's guidelines.

    Techniques: Derivative Assay, Infection, Plasmid Preparation, Expressing, Immunocytochemistry, Immunofluorescence, Western Blot

    Viability of breast cancer cells exposed to monotherapy or with a combination therapy of paclitaxel with salinomycin. (A) MDA-MB-231; (B) MCF-7 cells. Mean ± SD, n = 5. * P

    Journal: Cancer Biology & Therapy

    Article Title: Combination therapy targeting both cancer stem-like cells and bulk tumor cells for improved efficacy of breast cancer treatment

    doi: 10.1080/15384047.2016.1190488

    Figure Lengend Snippet: Viability of breast cancer cells exposed to monotherapy or with a combination therapy of paclitaxel with salinomycin. (A) MDA-MB-231; (B) MCF-7 cells. Mean ± SD, n = 5. * P

    Article Snippet: Salinomycin was purchased from Cayman Chemical; Paclitaxel was purchased from Cedarburg Pharmaceuticals, and lipodox was purchased from SUN Pharmaceutical Ind, Ltd. PE mouse anti-human CD44 and FITC Mouse Anti-Human CD24, FITC Mouse IG2a, k isotype control and PE Mouse IG2b, k isotype control were purchased from BD Sciences.

    Techniques: Multiple Displacement Amplification

    Effect of drug treatment on the formation of MCF-7 mammospheres. Salinomycin treatment inhibited the formation of mammospheres, while paclitaxel treatment generated mammospheres, which were smaller compared to the untreated group.

    Journal: Cancer Biology & Therapy

    Article Title: Combination therapy targeting both cancer stem-like cells and bulk tumor cells for improved efficacy of breast cancer treatment

    doi: 10.1080/15384047.2016.1190488

    Figure Lengend Snippet: Effect of drug treatment on the formation of MCF-7 mammospheres. Salinomycin treatment inhibited the formation of mammospheres, while paclitaxel treatment generated mammospheres, which were smaller compared to the untreated group.

    Article Snippet: Salinomycin was purchased from Cayman Chemical; Paclitaxel was purchased from Cedarburg Pharmaceuticals, and lipodox was purchased from SUN Pharmaceutical Ind, Ltd. PE mouse anti-human CD44 and FITC Mouse Anti-Human CD24, FITC Mouse IG2a, k isotype control and PE Mouse IG2b, k isotype control were purchased from BD Sciences.

    Techniques: Generated

    Taxol crystals resemble asters and bundles formed in the presence of Taxol-stabilized microtubules. (A) Two asters (top and middle) and one bundle (bottom) formed in the presence of Taxol and fluorescently labeled tubulin, as in text. Paired images with DIC (left) and fluorescent (right) optics. (B) DIC images of a Taxol crystal aster (top) and bundle (bottom), formed in the absence of tubulin. Bars, 10 µm.

    Journal: PLoS ONE

    Article Title: Taxol Crystals Can Masquerade as Stabilized Microtubules

    doi: 10.1371/journal.pone.0001476

    Figure Lengend Snippet: Taxol crystals resemble asters and bundles formed in the presence of Taxol-stabilized microtubules. (A) Two asters (top and middle) and one bundle (bottom) formed in the presence of Taxol and fluorescently labeled tubulin, as in text. Paired images with DIC (left) and fluorescent (right) optics. (B) DIC images of a Taxol crystal aster (top) and bundle (bottom), formed in the absence of tubulin. Bars, 10 µm.

    Article Snippet: Generation of Taxol-stabilized microtubules To promote microtubule assembly, 1.14 mg/ml Fluorescein-tubulin (Cytoskeleton) in BRB 80 buffer was incubated at 37°C for 20 minutes .

    Techniques: Labeling

    Taxol crystals bind fluorescently labeled tubulin subunits. (A) Fluorescently labeled tubulin (released from a micropipette to the left of the field) immediately accumulated on the preformed Taxol crystal aster, as shown in these sequential images. (B) An equilibrium solution of fluorescently labeled tubulin (green haze) and microtubules was released as in (A), and decorated a Taxol ‘bow-tie’ (i.e., nonspherical) crystal aster (half of aster is visible, in upper right). Again, the crystal was instantly labeled by subunits, which diffuse more rapidly than microtubules. Microtubules did not appear to contribute to the brightness of the tubulin-decorated crystal, as fluorescence intensity did not increase over time. Thus, microtubules did not appear to play a major role in decorating the Taxol crystal. The arrow tracks the path of a single microtubule that briefly made contact with the aster, but diffused away. The shallow aqueous puddle containing the crystal aster is outlined in the first panel. Time in seconds. Bars, 10 µm.

    Journal: PLoS ONE

    Article Title: Taxol Crystals Can Masquerade as Stabilized Microtubules

    doi: 10.1371/journal.pone.0001476

    Figure Lengend Snippet: Taxol crystals bind fluorescently labeled tubulin subunits. (A) Fluorescently labeled tubulin (released from a micropipette to the left of the field) immediately accumulated on the preformed Taxol crystal aster, as shown in these sequential images. (B) An equilibrium solution of fluorescently labeled tubulin (green haze) and microtubules was released as in (A), and decorated a Taxol ‘bow-tie’ (i.e., nonspherical) crystal aster (half of aster is visible, in upper right). Again, the crystal was instantly labeled by subunits, which diffuse more rapidly than microtubules. Microtubules did not appear to contribute to the brightness of the tubulin-decorated crystal, as fluorescence intensity did not increase over time. Thus, microtubules did not appear to play a major role in decorating the Taxol crystal. The arrow tracks the path of a single microtubule that briefly made contact with the aster, but diffused away. The shallow aqueous puddle containing the crystal aster is outlined in the first panel. Time in seconds. Bars, 10 µm.

    Article Snippet: Generation of Taxol-stabilized microtubules To promote microtubule assembly, 1.14 mg/ml Fluorescein-tubulin (Cytoskeleton) in BRB 80 buffer was incubated at 37°C for 20 minutes .

    Techniques: Labeling, Fluorescence

    Effects of paclitaxel loaded micelles on human breast tumor cell proliferation/viability determined by SRB method: a MDA-MB-231 cells. b T47D cells. Exponentially grown T47D and MDA-MB-231 cells were exposed to the different concentration of PTX-loaded

    Journal: The AAPS Journal

    Article Title: Novel Redox-Responsive Amphiphilic Copolymer Micelles for Drug Delivery: Synthesis and Characterization

    doi: 10.1208/s12248-015-9800-2

    Figure Lengend Snippet: Effects of paclitaxel loaded micelles on human breast tumor cell proliferation/viability determined by SRB method: a MDA-MB-231 cells. b T47D cells. Exponentially grown T47D and MDA-MB-231 cells were exposed to the different concentration of PTX-loaded

    Article Snippet: Paclitaxel (PTX) was purchased from LC Laboratories® (Woburn, MA).

    Techniques: Sulforhodamine B Assay, Multiple Displacement Amplification, Concentration Assay

    Plasma concentration–time curves for total paclitaxel at 1-h infusion of paclitaxel micellar at doses ranging between 90 and 275 mg/m 2 . a Mean concentrations for each dose level on a linear–linear scale, excluding the 90 mg dose ( n = 1) since it is outside the clinical dose range and mainly used to assess safety. b Individual (dots) and mean concentrations (continuous line) of data sets included in the PK evaluation, presented per dose level on log-linear scales. n number of data sets

    Journal: Advances in Therapy

    Article Title: Maximum Tolerated Dose and Pharmacokinetics of Paclitaxel Micellar in Patients with Recurrent Malignant Solid Tumours: A Dose-Escalation Study

    doi: 10.1007/s12325-019-00909-6

    Figure Lengend Snippet: Plasma concentration–time curves for total paclitaxel at 1-h infusion of paclitaxel micellar at doses ranging between 90 and 275 mg/m 2 . a Mean concentrations for each dose level on a linear–linear scale, excluding the 90 mg dose ( n = 1) since it is outside the clinical dose range and mainly used to assess safety. b Individual (dots) and mean concentrations (continuous line) of data sets included in the PK evaluation, presented per dose level on log-linear scales. n number of data sets

    Article Snippet: As a result of the absence of Cremophor, it was anticipated that hypersensitivity events would be less frequent with paclitaxel micellar.

    Techniques: Concentration Assay

    Mean C max of paclitaxel after 0.5-h infusions of paclitaxel micellar (orange squares) and nab-paclitaxel (empty circles, blue triangles) at various dose levels. Nab-paclitaxel data were extracted from six studies compiled by Stage et al. (empty circles; [ 14 ]) and one study by Nyman et al. (blue triangles; [ 15 ]). Number of patients per dose level of paclitaxel micellar was as follows: N = 2 (150 mg/m 2 ), N = 3 (175 mg/m 2 ), N = 4 (200 mg/m 2 ), N = 4 (225 mg/m 2 ), N = 5 (250 mg/m 2 ), N = 6 (275 mg/m 2 )

    Journal: Advances in Therapy

    Article Title: Maximum Tolerated Dose and Pharmacokinetics of Paclitaxel Micellar in Patients with Recurrent Malignant Solid Tumours: A Dose-Escalation Study

    doi: 10.1007/s12325-019-00909-6

    Figure Lengend Snippet: Mean C max of paclitaxel after 0.5-h infusions of paclitaxel micellar (orange squares) and nab-paclitaxel (empty circles, blue triangles) at various dose levels. Nab-paclitaxel data were extracted from six studies compiled by Stage et al. (empty circles; [ 14 ]) and one study by Nyman et al. (blue triangles; [ 15 ]). Number of patients per dose level of paclitaxel micellar was as follows: N = 2 (150 mg/m 2 ), N = 3 (175 mg/m 2 ), N = 4 (200 mg/m 2 ), N = 4 (225 mg/m 2 ), N = 5 (250 mg/m 2 ), N = 6 (275 mg/m 2 )

    Article Snippet: As a result of the absence of Cremophor, it was anticipated that hypersensitivity events would be less frequent with paclitaxel micellar.

    Techniques:

    Relationship between given dose and a mean C max or b mean AUC inf after a 1-h infusion for doses between 150 mg/m 2 and 275 mg/m 2 of paclitaxel micellar

    Journal: Advances in Therapy

    Article Title: Maximum Tolerated Dose and Pharmacokinetics of Paclitaxel Micellar in Patients with Recurrent Malignant Solid Tumours: A Dose-Escalation Study

    doi: 10.1007/s12325-019-00909-6

    Figure Lengend Snippet: Relationship between given dose and a mean C max or b mean AUC inf after a 1-h infusion for doses between 150 mg/m 2 and 275 mg/m 2 of paclitaxel micellar

    Article Snippet: As a result of the absence of Cremophor, it was anticipated that hypersensitivity events would be less frequent with paclitaxel micellar.

    Techniques:

    The anti-tumor efficacy after intraperitoneal therapy of different PTX formulations and noninvasive bioluminescence imaging in a murine model of peritoneally disseminated ovarian cancer. (A) Bioluminescence emitted by luciferase-expressing SKOV3-luc cancer cells at different time points after treatment. Peritoneal SKOV3-luc tumors bearing mice received total five intraperitoneal injection of Taxol®, Abraxane® and PTX-PEG 5k -CA 8 NPs on day 0, 4, 8, 12 and 16. Control groups received PBS only. Signal from the entire abdominal region of each mouse were quantified, and background was subtracted by measuring same sized ROIs in areas without light emission. (B) Survival of mice in different treatment groups. Open circle represents censored data point secondary to a death during anesthesia (i.e., not tumor-related). (C) Representative pseudocolor images of intraperitoneal tumor burden. Color scale minimum and maximum have been adjusted so that they are identical in each image.

    Journal: Biomaterials

    Article Title: A self-assembling nanoparticle for paclitaxel delivery in ovarian cancer

    doi: 10.1016/j.biomaterials.2009.07.015

    Figure Lengend Snippet: The anti-tumor efficacy after intraperitoneal therapy of different PTX formulations and noninvasive bioluminescence imaging in a murine model of peritoneally disseminated ovarian cancer. (A) Bioluminescence emitted by luciferase-expressing SKOV3-luc cancer cells at different time points after treatment. Peritoneal SKOV3-luc tumors bearing mice received total five intraperitoneal injection of Taxol®, Abraxane® and PTX-PEG 5k -CA 8 NPs on day 0, 4, 8, 12 and 16. Control groups received PBS only. Signal from the entire abdominal region of each mouse were quantified, and background was subtracted by measuring same sized ROIs in areas without light emission. (B) Survival of mice in different treatment groups. Open circle represents censored data point secondary to a death during anesthesia (i.e., not tumor-related). (C) Representative pseudocolor images of intraperitoneal tumor burden. Color scale minimum and maximum have been adjusted so that they are identical in each image.

    Article Snippet: Taxol® (Mayne Pharma, Paramus, NJ) and Abraxane® (Abraxis Bioscience, LA, CA) were obtained from a hospital pharmacy.

    Techniques: Imaging, Luciferase, Expressing, Mouse Assay, Injection

    The cytotoxicity of PEG 5k -CA 8 nanoparticles with or without PTX loading against normal human cells and ovarian cancer cells. (A) Cytotoxicity of blank PEG 5k -CA 8 NPs and cremophor:ethanol vehicle on HFF1 human fibroblast cells. C 1 and C 2 are the estimated blood concentratoin of PEG 5k -CA 8 and cremophor:ethanol after in vivo administration, respectively, assuming the blood volume of an average person is 6L. The anticancer effects of PTX-loaded PEG 5k -CA 8 NPs were performed on ES-2 cells (B) and SKOV3-luc cells (C) compared with Taxol®and Abraxane®.

    Journal: Biomaterials

    Article Title: A self-assembling nanoparticle for paclitaxel delivery in ovarian cancer

    doi: 10.1016/j.biomaterials.2009.07.015

    Figure Lengend Snippet: The cytotoxicity of PEG 5k -CA 8 nanoparticles with or without PTX loading against normal human cells and ovarian cancer cells. (A) Cytotoxicity of blank PEG 5k -CA 8 NPs and cremophor:ethanol vehicle on HFF1 human fibroblast cells. C 1 and C 2 are the estimated blood concentratoin of PEG 5k -CA 8 and cremophor:ethanol after in vivo administration, respectively, assuming the blood volume of an average person is 6L. The anticancer effects of PTX-loaded PEG 5k -CA 8 NPs were performed on ES-2 cells (B) and SKOV3-luc cells (C) compared with Taxol®and Abraxane®.

    Article Snippet: Taxol® (Mayne Pharma, Paramus, NJ) and Abraxane® (Abraxis Bioscience, LA, CA) were obtained from a hospital pharmacy.

    Techniques: In Vivo

    In vivo anti-tumor efficacy (A) and body weight changes (B) after intravenous treatment of different PTX formulations in the subcutaneous mouse model of SKOV3-luc ovarian cancer. Tumor bearing mice were administered i.v. with PBS (control), Taxol®, Abraxane® and PTX-PEG 5k -CA 8 NPs on days 0, 4, 8 and days 38, 42, 46 when tumor volume reached about 100~200 mm 3 . Data represent mean ± SEM of six mice per group.

    Journal: Biomaterials

    Article Title: A self-assembling nanoparticle for paclitaxel delivery in ovarian cancer

    doi: 10.1016/j.biomaterials.2009.07.015

    Figure Lengend Snippet: In vivo anti-tumor efficacy (A) and body weight changes (B) after intravenous treatment of different PTX formulations in the subcutaneous mouse model of SKOV3-luc ovarian cancer. Tumor bearing mice were administered i.v. with PBS (control), Taxol®, Abraxane® and PTX-PEG 5k -CA 8 NPs on days 0, 4, 8 and days 38, 42, 46 when tumor volume reached about 100~200 mm 3 . Data represent mean ± SEM of six mice per group.

    Article Snippet: Taxol® (Mayne Pharma, Paramus, NJ) and Abraxane® (Abraxis Bioscience, LA, CA) were obtained from a hospital pharmacy.

    Techniques: In Vivo, Mouse Assay

    Histological evidence of delayed healing and necrotic core strut penetration in drug eluting stented saphenous vein grafts (A) A 84-year-old women received two overlapping paclitaxel eluting Taxus stent implanted 2 years antemortem demonstrates stent strut penetration into the lipid-rich necrotic core (NC) region. The fibrous cap (green arrow) is shown to have been disrupted by the stent struts (*-stent strut). (B) In the overlapping region, struts are uncovered but are surrounded by a thin layer of thrombus (Thr) primarily composed of fibrin. (C) In the distal region, struts are surrounded by a thin layer of thrombus.

    Journal: JACC. Cardiovascular interventions

    Article Title: Pathology of Drug-Eluting Versus Bare Metal Stents in Saphenous Vein Bypass Graft Lesions

    doi: 10.1016/j.jcin.2011.12.017

    Figure Lengend Snippet: Histological evidence of delayed healing and necrotic core strut penetration in drug eluting stented saphenous vein grafts (A) A 84-year-old women received two overlapping paclitaxel eluting Taxus stent implanted 2 years antemortem demonstrates stent strut penetration into the lipid-rich necrotic core (NC) region. The fibrous cap (green arrow) is shown to have been disrupted by the stent struts (*-stent strut). (B) In the overlapping region, struts are uncovered but are surrounded by a thin layer of thrombus (Thr) primarily composed of fibrin. (C) In the distal region, struts are surrounded by a thin layer of thrombus.

    Article Snippet: Reduced restenosis rates associated with sirolimus (SES, Cypher, Cordis Johnson & Johnson, Miami, FL) and paclitaxel (PES, Taxus, Boston Scientific Corporation, Boston, MA) drug eluting stents in native coronary arteries has resulted in the frequent use of DES in atherosclerotic SVBGs ( , ).

    Techniques:

    Atherosclerotic change in saphenous vein grafts following stenting (A–B) A paclitaxel eluting Taxus stent implanted five months antemortem in an 84-year-old women demonstrates foamy macrophages within the neointimal layer (*-stent strut). (C–D) A bare metal Multi-Link Vision stent implanted 3 years antemortem in a 66-year-old man shows foamy macrophages within the neointimal layer.

    Journal: JACC. Cardiovascular interventions

    Article Title: Pathology of Drug-Eluting Versus Bare Metal Stents in Saphenous Vein Bypass Graft Lesions

    doi: 10.1016/j.jcin.2011.12.017

    Figure Lengend Snippet: Atherosclerotic change in saphenous vein grafts following stenting (A–B) A paclitaxel eluting Taxus stent implanted five months antemortem in an 84-year-old women demonstrates foamy macrophages within the neointimal layer (*-stent strut). (C–D) A bare metal Multi-Link Vision stent implanted 3 years antemortem in a 66-year-old man shows foamy macrophages within the neointimal layer.

    Article Snippet: Reduced restenosis rates associated with sirolimus (SES, Cypher, Cordis Johnson & Johnson, Miami, FL) and paclitaxel (PES, Taxus, Boston Scientific Corporation, Boston, MA) drug eluting stents in native coronary arteries has resulted in the frequent use of DES in atherosclerotic SVBGs ( , ).

    Techniques: