gemcitabine Search Results


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  • 99
    Millipore gemcitabine
    Increase in Rad51 foci after PARP inhibition or <t>gemcitabine</t> treatment in TNBC cells
    Gemcitabine, supplied by Millipore, used in various techniques. Bioz Stars score: 99/100, based on 1364 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    88
    Eli Lilly gemcitabine gemzar
    Anti-tumor effects of combination therapy with VEGF-Trap and <t>gemcitabine</t> in LLC tumor model. ( A ) Bioluminescence images of subcutaneous inoculated LLC tumors on day 12 after the start of treatment; ( B ) Imaging analysis (photons per second) depicting the tumor volumes of mice using the IndiGo imaging analysis software; ( C ) Tumor volume calculated on day 3, 6, 9, 12,15 after the start of treatment; ( D ) Representative tumor photos on day 15 after the start of treatment; ( E ) Tumor weights were measured on day 15 when tumors were harvested; ( F ) Survival curves were constructed according to the Kaplan-Meier analysis. n = 8 for each group, * P
    Gemcitabine Gemzar, supplied by Eli Lilly, used in various techniques. Bioz Stars score: 88/100, based on 109 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    93
    Tocris gemcitabine hcl gemzar
    Effects of compound treatment on mitochondrial mass and cell size. HT29 cells were treated with the indicated drugs for 48 hours. (Aphidicolin; 3.1 µM, Etoposide; 3.9 µM, <t>Gemcitabine;</t> 24 nM, Paclitaxel; 98 nM, VX-680; 195, nM, PD901; 390 nM). A. Images of Hoechst 33452-stained DNA (red) and MitoTracker deep red-FM staining (green) were acquired with a 20x water-immersion objective as described in Methods section. All images are shown at same magnification and intensity scaling. Scale bar = 50 µm. B. MitoTracker deep red images showing identification and segmentation of cell boundaries. C. Scatter plots and histograms of log2-normalized integrated DNA intensity (x axis, upper histogram panels) and integrated cytoplasmic MitoTracker Deep Red FM staining intensity (y axis, right-side histograms) derived from the same wells as shown in part A. D. Variation in cell area and mitochondrial content (integrated MitoTracker deep red intensity) for the same cell populations, normalized as fold change relative to the mean area and intensity of DMSO-treated samples.
    Gemcitabine Hcl Gemzar, supplied by Tocris, used in various techniques. Bioz Stars score: 93/100, based on 3 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    93
    Eli Lilly gemcitabine gemzar drug
    Reduced miR-30a expression correlates with tumor progression and lower patient survival rate in pancreatic cancers. a MiR-30a expression in tumor and adjacent normal pancreatic tissues was determined using qRT-PCR (88 pancreatic cancer samples and 88 normal pancreatic tissues). Error bars, ±SEM. b SNAI1 gene expression in tumor and adjacent normal pancreatic tissues was determined using qRT-PCR (88 pancreatic cancer samples and 88 normal pancreatic tissues, as shown in a ). Error bars, ±SEM. c Representative miR-30a expression in tumor and normal pancreatic tissues was determined using qRT-PCR (12 pancreatic cancer samples and 12 normal pancreatic tissues). Error bars, ±SEM. d Correlation study of miR-30a and SNAI1 in pancreatic carcinoma. Statistical analyses were performed with the χ 2 test. R , Pearson correlation coefficient. e Correlation study between miR-30a level and <t>gemcitabine</t> response in pancreatic carcinoma with the χ 2 test. R , Pearson correlation coefficient. f Association between miR-30a expression level and overall survival rate analyzed by the Kaplan–Meier method. Patients were split into high and low expression groups based on the median expression of the miR-30a. g Evaluation of tumor growth for xenograft mouse models of pancreatic cancer. Mice were inoculated subcutaneously in the right flank with 0.1 ml matrigel containing 2 × 10 6 cells. Representative images of tumor were captured at the end of 3 weeks. n = 5 per group. h Gemcitabine response in miR-Con or miR-30a xenograft mice. Results are represented by the tumor volume measured at each time point normalized to day 0. Data are presented as means ± SEM ( n = 5 per group). i MiR-30a xenografts are sensitive to gemcitabine in vivo. Results are represented by tumor inhibition ratio, calculated as follows: tumor volume at each time point normalized to day 0 for gemcitabine treated mice, corrected for that of vehicle group mice. * P
    Gemcitabine Gemzar Drug, supplied by Eli Lilly, used in various techniques. Bioz Stars score: 93/100, based on 2 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    97
    Selleck Chemicals gemcitabine
    Concentration-dependent cytotoxic effect of <t>gemcitabine</t> or cisplatin. a : KMBC (blue circles) and HuCCT1 (purple squares) cells and b : haploid BAP1 knockout (HAP1 BAP1 KO) ( green circles ) or parental haploid HAP1 cells (WT) ( orange squares ) were plated in 384-well plates (1,000 cells/well), and incubated with varying concentrations of gemcitabine or cisplatin. Cell viability was assessed after 72 h using Cell Titer GloR 2.0 assay. Data represents the average percent cell viability plotted against concentration of drug in nM from 4 replicates for each condition. The table indicates the inhibitory concentration at 50% effect (IC50) values for each drug for each of the cell lines
    Gemcitabine, supplied by Selleck Chemicals, used in various techniques. Bioz Stars score: 97/100, based on 225 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    92
    LKT Laboratories gemcitabine
    <t>Gemcitabine</t> depletion of IMC population prevents boney union in segmental defect A) Gemcitabine treatment results in significant depletion of Gr-1+CD11b+ IMC. B) H E staining and radiography of unhealed area in femoral segmental defect in wild-type mice (top) and gemcitabine treated mice (bottom) at 21 days post fracture. Relative quantitation of unhealed area following gemcitabine treatment, as compared to control is given on the right. Black arrows indicate fracture site, and failure to heal in gemcitabine-treated mice. (P
    Gemcitabine, supplied by LKT Laboratories, used in various techniques. Bioz Stars score: 92/100, based on 24 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    90
    Amgen gemcitabine
    <t>Gemcitabine</t> depletion of IMC population prevents boney union in segmental defect A) Gemcitabine treatment results in significant depletion of Gr-1+CD11b+ IMC. B) H E staining and radiography of unhealed area in femoral segmental defect in wild-type mice (top) and gemcitabine treated mice (bottom) at 21 days post fracture. Relative quantitation of unhealed area following gemcitabine treatment, as compared to control is given on the right. Black arrows indicate fracture site, and failure to heal in gemcitabine-treated mice. (P
    Gemcitabine, supplied by Amgen, used in various techniques. Bioz Stars score: 90/100, based on 5 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    92
    Enzo Biochem gemcitabine
    NL induces higher levels of caspase activity compared to current PDAC therapeutic agents MIA PaCa-2 and BXPC-3 cells were treated with 5 µM NL, 5 µM Sorafenib (SRF), 5 µM <t>Gemcitabine</t> (GMC), or 5 µM Curcumin (CUR). (A–C) Caspase-3, -8 and -9 activities in MIA PaCa-2 cells after 24 h of NL, SRF, and GMC treatment. (D) Caspase-3 activity in BXPC-3 cells after 24 h of NL, SRF, and GMC treatment. (E) Caspase-3 activity in MIA PaCa-2 cells after 24 h of NL and CUR treatment. (F) Images of RWPE-1, MIA PaCa-2, and BXPC-3 cells treated with NL for 24 h and 48 h. Data are mean ± SD, n = 3 and presented as fold-change compared to respective controls. Statistical significance was determined by a t-test: *p
    Gemcitabine, supplied by Enzo Biochem, used in various techniques. Bioz Stars score: 92/100, based on 4 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    93
    FUJIFILM gemcitabine
    Drug sensitivity test in BAP1 knockdown GBC cell line. Cell viability of BAP1 knocked-down GBC cell line G-415 under the agents of <t>gemcitabine</t> (GEM), cisplatin (CDDP), fluorouracil (5-FU), sodium valproate, 5-azacytidine, and bortezomib was measured by MTS assay. No change in sensitivity was observed in GEM, CDDP, 5-FU, sodium valproate or 5-azacytidine. Bortezomib showed a significant decrease in sensitivity in the siRNA1 and siRNA2 group compared to the control.
    Gemcitabine, supplied by FUJIFILM, used in various techniques. Bioz Stars score: 93/100, based on 62 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    92
    Hospira gemcitabine
    Body weight change of animals treated with TH-302 (T) in combination with <t>gemcitabine</t> (G) and nab-paclitaxel (nP) in tumor-bearing immunocomprised mice and immunocompetent mice. T was given at 50 mg/kg, ip, G was given at 60 mg/kg ip and nP was given at 30 mg/kg, iv; all drugs were dosed at a Q3Dx5 regimen. ( A - D ), in Hs766t, MIA PaCa-2, PANC-1 and BxPC-3 tumor-bearing nu/nu mice, respectively, n = 10 per group; ( E ), in CD-1 female mice, n = 6 per group; and ( F ), in CD-1 male mice, n = 10 per group. Data represent Mean ± SEM. Arrow, dosing time.
    Gemcitabine, supplied by Hospira, 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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    92
    LC Laboratories gemcitabine
    SLC7A11-AS1 Scavenges ROS to Promote Cancer Stemness (A–C) Effects of SLC7A11-AS1 knockdown on expressions of Oct4 and Nanog were determined by qRT-PCR (A and B) and western blot (C) in <t>gemcitabine-resistant</t> PDAC cells (n = 3). (D) Expressions of Oct4 and Nanog in tumor tissues (as described in Figure 1 G) were determined by western blot (D). (E) Oncosphere-formation assay in SLC7A11-AS1 -knockdown and control gemcitabine-resistant PDAC cells. Original magnification ×10. (F) qRT-PCR analysis of SLC7A11-AS1 expression in spheroids and paired attached PDAC cells (n = 3). (G) Flow cytometry analysis of ROS using probe DCFH-DA (upper) and western blot analysis of Oct4 and Nanog (bottom) in SLC7A11-AS1 -knockdown and control PANC-1 cells treated with or without NAC (10 mM) for 48 h (n = 3). *p
    Gemcitabine, supplied by LC Laboratories, used in various techniques. Bioz Stars score: 92/100, based on 121 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    93
    Merck KGaA gemcitabine
    Therapeutic efficacy of <t>Gemcitabine</t> combined with iRGD for human NSCLC xenografts. (A) The tumor volume curve during treatment. Arrows indicate the time of injection. The day when treatment started was recorded as day 0. Tumor volume was measured once every three days until day 30. (B) Average tumor weight of each group at the end of treatment. (C) The body weight shift curve of the mice during the experiment. n = 6. Error bars, mean ± SD; ns, not significant; *** p
    Gemcitabine, supplied by Merck KGaA, used in various techniques. Bioz Stars score: 93/100, based on 43 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    92
    Santa Cruz Biotechnology gemcitabine
    Figure 6. Alterations in cell viability using SGI-1776 combination therapy with <t>gemcitabine-based</t> chemotherapy in pancreatic cancer cells. To evaluate the combination of SGI-1776 and gemcitabine on cell viability, PANC-1 ( A ) and MIA PaCa-2 ( B
    Gemcitabine, supplied by Santa Cruz Biotechnology, used in various techniques. Bioz Stars score: 92/100, based on 41 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    90
    Cayman Chemical gemcitabine
    D5D- KD and DGLA treatment enhanced efficacy of <t>gemcitabine</t> on cell migration and invasion in BxPC-3 cells. A) Transwell migration assay of D5D- KD BxPC-3 cells upon treatment of DGLA (100 µM), gemcitabine (0.1 µM) alone or gemcitabine+DGLA. The D5D- KD cells without fatty acid and drug treatment were used as controls; B) Transwell invasion assay of D5D- KD BxPC-3 cells upon treatment of DGLA (100 µM), gemcitabine (0.1 µM) alone or gemcitabine+DGLA. The D5D- KD cells without fatty acid and drug treatment were used as controls; C) Western blot and protein expression level of acetyl histone H3, MMP-2, MMP-9, E-cadherin, vimentin and snail from D5D- KD BxPC-3 cells treated with vehicle (control), DGLA (100 μM), gemcitabine (0.1 μM) or gemcitabine+DGLA. Protein expression rate was normalized using β-actin as loading control (*: significant difference vs. control with p
    Gemcitabine, supplied by Cayman Chemical, used in various techniques. Bioz Stars score: 90/100, based on 40 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Image Search Results


    Increase in Rad51 foci after PARP inhibition or gemcitabine treatment in TNBC cells

    Journal: Cancer research

    Article Title: Synergistic chemosensitivity of triple-negative breast cancer cell lines to PARP inhibition, gemcitabine and cisplatin

    doi: 10.1158/0008-5472.CAN-09-4521

    Figure Lengend Snippet: Increase in Rad51 foci after PARP inhibition or gemcitabine treatment in TNBC cells

    Article Snippet: Cells were plated overnight in chambered slides followed by treatment with either 10 μM PJ34, 0.6 nM gemcitabine or 4 μM cisplatin for 24 h. For Annexin V-FITC, standard manufacturers protocol was followed (Sigma).

    Techniques: Inhibition

    Synergism between PJ34 and gemcitabine or cisplatin

    Journal: Cancer research

    Article Title: Synergistic chemosensitivity of triple-negative breast cancer cell lines to PARP inhibition, gemcitabine and cisplatin

    doi: 10.1158/0008-5472.CAN-09-4521

    Figure Lengend Snippet: Synergism between PJ34 and gemcitabine or cisplatin

    Article Snippet: Cells were plated overnight in chambered slides followed by treatment with either 10 μM PJ34, 0.6 nM gemcitabine or 4 μM cisplatin for 24 h. For Annexin V-FITC, standard manufacturers protocol was followed (Sigma).

    Techniques:

    Cell viability of PARP1 and PARP2 knockdown cells after gemcitabine and cisplatin treatment

    Journal: Cancer research

    Article Title: Synergistic chemosensitivity of triple-negative breast cancer cell lines to PARP inhibition, gemcitabine and cisplatin

    doi: 10.1158/0008-5472.CAN-09-4521

    Figure Lengend Snippet: Cell viability of PARP1 and PARP2 knockdown cells after gemcitabine and cisplatin treatment

    Article Snippet: Cells were plated overnight in chambered slides followed by treatment with either 10 μM PJ34, 0.6 nM gemcitabine or 4 μM cisplatin for 24 h. For Annexin V-FITC, standard manufacturers protocol was followed (Sigma).

    Techniques:

    Decreased NER in TNBC cells after PARP inhibition or gemcitabine treatment

    Journal: Cancer research

    Article Title: Synergistic chemosensitivity of triple-negative breast cancer cell lines to PARP inhibition, gemcitabine and cisplatin

    doi: 10.1158/0008-5472.CAN-09-4521

    Figure Lengend Snippet: Decreased NER in TNBC cells after PARP inhibition or gemcitabine treatment

    Article Snippet: Cells were plated overnight in chambered slides followed by treatment with either 10 μM PJ34, 0.6 nM gemcitabine or 4 μM cisplatin for 24 h. For Annexin V-FITC, standard manufacturers protocol was followed (Sigma).

    Techniques: Inhibition

    DNA damage in cells after PARP inhibition or gemcitabine treatment

    Journal: Cancer research

    Article Title: Synergistic chemosensitivity of triple-negative breast cancer cell lines to PARP inhibition, gemcitabine and cisplatin

    doi: 10.1158/0008-5472.CAN-09-4521

    Figure Lengend Snippet: DNA damage in cells after PARP inhibition or gemcitabine treatment

    Article Snippet: Cells were plated overnight in chambered slides followed by treatment with either 10 μM PJ34, 0.6 nM gemcitabine or 4 μM cisplatin for 24 h. For Annexin V-FITC, standard manufacturers protocol was followed (Sigma).

    Techniques: Inhibition

    Cell viability of breast cancer cells after PJ34, gemcitabine or cisplatin treatment

    Journal: Cancer research

    Article Title: Synergistic chemosensitivity of triple-negative breast cancer cell lines to PARP inhibition, gemcitabine and cisplatin

    doi: 10.1158/0008-5472.CAN-09-4521

    Figure Lengend Snippet: Cell viability of breast cancer cells after PJ34, gemcitabine or cisplatin treatment

    Article Snippet: Cells were plated overnight in chambered slides followed by treatment with either 10 μM PJ34, 0.6 nM gemcitabine or 4 μM cisplatin for 24 h. For Annexin V-FITC, standard manufacturers protocol was followed (Sigma).

    Techniques:

    Combinatorial effect of αM or γM with gemcitabine against pancreatic cancer cells. To evaluate IC 50 of gemcitabine, MIA PaCa-2 (A) and PANC-1 (B) were treated with gemcitabine for 72 h. Gemcitabine in combination with αM (C, D) or γM (E, F) were added to MIA PaCa-2 (C, E) or PANC-1 (D, F) at a constant rate based on each IC 50 value. After incubation for 72 h, cell viability was measured using WST-1 reagent and calculated from mean values of three wells. This experiment was repeated three times. CI value was calculated for combinatorial effect (G). * p

    Journal: Biomolecules & Therapeutics

    Article Title: α, γ-Mangostins Induce Autophagy and Show Synergistic Effect with Gemcitabine in Pancreatic Cancer Cell Lines

    doi: 10.4062/biomolther.2017.074

    Figure Lengend Snippet: Combinatorial effect of αM or γM with gemcitabine against pancreatic cancer cells. To evaluate IC 50 of gemcitabine, MIA PaCa-2 (A) and PANC-1 (B) were treated with gemcitabine for 72 h. Gemcitabine in combination with αM (C, D) or γM (E, F) were added to MIA PaCa-2 (C, E) or PANC-1 (D, F) at a constant rate based on each IC 50 value. After incubation for 72 h, cell viability was measured using WST-1 reagent and calculated from mean values of three wells. This experiment was repeated three times. CI value was calculated for combinatorial effect (G). * p

    Article Snippet: Combination study with gemcitabine Gemcitabine was purchased from Sigma-Aldrich (St. Louis, Mo, USA) and dissolved in DMSO at 10 mM.

    Techniques: Incubation

    Anti-tumor effects of combination therapy with VEGF-Trap and gemcitabine in LLC tumor model. ( A ) Bioluminescence images of subcutaneous inoculated LLC tumors on day 12 after the start of treatment; ( B ) Imaging analysis (photons per second) depicting the tumor volumes of mice using the IndiGo imaging analysis software; ( C ) Tumor volume calculated on day 3, 6, 9, 12,15 after the start of treatment; ( D ) Representative tumor photos on day 15 after the start of treatment; ( E ) Tumor weights were measured on day 15 when tumors were harvested; ( F ) Survival curves were constructed according to the Kaplan-Meier analysis. n = 8 for each group, * P

    Journal: PLoS ONE

    Article Title: Combination Therapy of VEGF-Trap and Gemcitabine Results in Improved Anti-Tumor Efficacy in a Mouse Lung Cancer Model

    doi: 10.1371/journal.pone.0068589

    Figure Lengend Snippet: Anti-tumor effects of combination therapy with VEGF-Trap and gemcitabine in LLC tumor model. ( A ) Bioluminescence images of subcutaneous inoculated LLC tumors on day 12 after the start of treatment; ( B ) Imaging analysis (photons per second) depicting the tumor volumes of mice using the IndiGo imaging analysis software; ( C ) Tumor volume calculated on day 3, 6, 9, 12,15 after the start of treatment; ( D ) Representative tumor photos on day 15 after the start of treatment; ( E ) Tumor weights were measured on day 15 when tumors were harvested; ( F ) Survival curves were constructed according to the Kaplan-Meier analysis. n = 8 for each group, * P

    Article Snippet: Gemcitabine (Gemzar) was kindly supplied by Eli Lilly (Indianapolis, Ind., USA) and stored at 4°C.

    Techniques: Imaging, Mouse Assay, Software, Construct

    Down-regulation of proteins associated with proliferation, anti-apoptosis and invasion in tumor after the combination therapy. ( A ) Western blot analysis showed that VEGF-Trap combined with gemcitabine inhibited the expression of Cyclin D1, Pro-Caspase-3, Bcl-2, MMP2 and MMP9 in LLC tumors; ( B ) Quantitation of protein levels. β-actin served as an internal control. Densitometer quantitation was relative to the first data set in each case (indicated by a value of 1). All data are representative of at least two independent experiments. * P

    Journal: PLoS ONE

    Article Title: Combination Therapy of VEGF-Trap and Gemcitabine Results in Improved Anti-Tumor Efficacy in a Mouse Lung Cancer Model

    doi: 10.1371/journal.pone.0068589

    Figure Lengend Snippet: Down-regulation of proteins associated with proliferation, anti-apoptosis and invasion in tumor after the combination therapy. ( A ) Western blot analysis showed that VEGF-Trap combined with gemcitabine inhibited the expression of Cyclin D1, Pro-Caspase-3, Bcl-2, MMP2 and MMP9 in LLC tumors; ( B ) Quantitation of protein levels. β-actin served as an internal control. Densitometer quantitation was relative to the first data set in each case (indicated by a value of 1). All data are representative of at least two independent experiments. * P

    Article Snippet: Gemcitabine (Gemzar) was kindly supplied by Eli Lilly (Indianapolis, Ind., USA) and stored at 4°C.

    Techniques: Western Blot, Expressing, Quantitation Assay

    Effect of VEGF-Trap combined with gemcitabine on cell apoptosis within tumors. ( A ) Cell apoptosis was evaluated by TUNEL staining, the representative sections of LLC tumor tissues were obtained from mice on day 15 after treatment initiation; ( B ) The apoptotic index was determined as described in “Materials and methods”. * P

    Journal: PLoS ONE

    Article Title: Combination Therapy of VEGF-Trap and Gemcitabine Results in Improved Anti-Tumor Efficacy in a Mouse Lung Cancer Model

    doi: 10.1371/journal.pone.0068589

    Figure Lengend Snippet: Effect of VEGF-Trap combined with gemcitabine on cell apoptosis within tumors. ( A ) Cell apoptosis was evaluated by TUNEL staining, the representative sections of LLC tumor tissues were obtained from mice on day 15 after treatment initiation; ( B ) The apoptotic index was determined as described in “Materials and methods”. * P

    Article Snippet: Gemcitabine (Gemzar) was kindly supplied by Eli Lilly (Indianapolis, Ind., USA) and stored at 4°C.

    Techniques: TUNEL Assay, Staining, Mouse Assay

    Cumulative in situ release of gemcitabine from PolyGem at pH 5.0 and 7.4 and 37°C, as measured via UV/V is spectroscopy for 7 days. n = 3 for each data point and error bars represent standard deviation.

    Journal: Journal of pharmaceutics

    Article Title: Biodegradable Polymersomes for the Delivery of Gemcitabine to Panc-1 Cells

    doi: 10.1155/2013/932797

    Figure Lengend Snippet: Cumulative in situ release of gemcitabine from PolyGem at pH 5.0 and 7.4 and 37°C, as measured via UV/V is spectroscopy for 7 days. n = 3 for each data point and error bars represent standard deviation.

    Article Snippet: Materials Gemcitabine (Gemzar) was obtained from Eli Lilly and Company (Indianapolis, IN).

    Techniques: In Situ, Spectroscopy, Standard Deviation

    Schematic representation of PolyGem. In aqueous solution, poly(ethylene oxide)-b-poly(caprolactone) (PEO-PCL) self-assemble into spherical polymer vesicles (polymersomes), with the hydrophobic PCL chains orienting end to end to form the bilayer. The figure represents a uniaxial cross section of the polymersome, with gemcitabine ( ) encapsulated in the aqueous lumen. Vesicles can also be made to include PZn 3 (○) in the hydrophobic membrane.

    Journal: Journal of pharmaceutics

    Article Title: Biodegradable Polymersomes for the Delivery of Gemcitabine to Panc-1 Cells

    doi: 10.1155/2013/932797

    Figure Lengend Snippet: Schematic representation of PolyGem. In aqueous solution, poly(ethylene oxide)-b-poly(caprolactone) (PEO-PCL) self-assemble into spherical polymer vesicles (polymersomes), with the hydrophobic PCL chains orienting end to end to form the bilayer. The figure represents a uniaxial cross section of the polymersome, with gemcitabine ( ) encapsulated in the aqueous lumen. Vesicles can also be made to include PZn 3 (○) in the hydrophobic membrane.

    Article Snippet: Materials Gemcitabine (Gemzar) was obtained from Eli Lilly and Company (Indianapolis, IN).

    Techniques:

    Number of thrombocytes during 3 cycles of Gemzar chemotherapy

    Journal: Contemporary Oncology

    Article Title: Thrombocytosis in patients with pancreatic cancer treated with gemcitabine - does it have clinical significance? Description of 6 cases

    doi: 10.5114/wo.2012.30068

    Figure Lengend Snippet: Number of thrombocytes during 3 cycles of Gemzar chemotherapy

    Article Snippet: Case description The description refers to six patients receiving gemcitabine (Gemzar, Eli Lilly) in a standard dose of 1000 mg/m2 on the 1st , 8th and 15th day of a 28-day cycle (one patient was subjected to combined treatment with erlotinib 100 mg/d) for pancreatic cancer, treated in the Department of Haematology and Oncology, Medical University of Warsaw in 2010, who demonstrated thrombocytosis after administration of Gemzar.

    Techniques:

    Hemoglobin concentration during 3 cycles of Gemzar chemo - therapy

    Journal: Contemporary Oncology

    Article Title: Thrombocytosis in patients with pancreatic cancer treated with gemcitabine - does it have clinical significance? Description of 6 cases

    doi: 10.5114/wo.2012.30068

    Figure Lengend Snippet: Hemoglobin concentration during 3 cycles of Gemzar chemo - therapy

    Article Snippet: Case description The description refers to six patients receiving gemcitabine (Gemzar, Eli Lilly) in a standard dose of 1000 mg/m2 on the 1st , 8th and 15th day of a 28-day cycle (one patient was subjected to combined treatment with erlotinib 100 mg/d) for pancreatic cancer, treated in the Department of Haematology and Oncology, Medical University of Warsaw in 2010, who demonstrated thrombocytosis after administration of Gemzar.

    Techniques: Concentration Assay

    Pharmacodynamic evidence of in vivo for synergy between gemcitabine and carboplatin NSG mice were implanted with tumor model A and B) BL0645 or C and D) BL0269. Animals were dosed via tail vein injection of A and C) 0.375 mg/kg carboplatin (50,000 dpm/g), or 0.375 mg/kg carboplatin (50,000 dpm/g) plus 0.092 mg/kg gemcitabine, B, D) 0.092 mg/kg gemcitabine (1,000 dpm/g), or 0.092 mg/kg gemcitabine (1,000 dpm/g) plus 0.375 mg/kg carboplatin. Tumors were collected after 24h and isolated DNA was analyzed via AMS (N ≥ 3). Student's t-test was used to measure all p values. Presented are means and error bars represent SEM.

    Journal: Molecular cancer therapeutics

    Article Title: Microdose-induced Drug-DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice

    doi: 10.1158/1535-7163.MCT-16-0381

    Figure Lengend Snippet: Pharmacodynamic evidence of in vivo for synergy between gemcitabine and carboplatin NSG mice were implanted with tumor model A and B) BL0645 or C and D) BL0269. Animals were dosed via tail vein injection of A and C) 0.375 mg/kg carboplatin (50,000 dpm/g), or 0.375 mg/kg carboplatin (50,000 dpm/g) plus 0.092 mg/kg gemcitabine, B, D) 0.092 mg/kg gemcitabine (1,000 dpm/g), or 0.092 mg/kg gemcitabine (1,000 dpm/g) plus 0.375 mg/kg carboplatin. Tumors were collected after 24h and isolated DNA was analyzed via AMS (N ≥ 3). Student's t-test was used to measure all p values. Presented are means and error bars represent SEM.

    Article Snippet: Unlabeled gemcitabine (GEMZAR®) was obtained from Eli Lilly (Indianapolis, IN, USA), and carboplatin (CARBOplatin®, 10 mg/mL) from Hospira (Lake Forest, IL, USA).

    Techniques: In Vivo, Mouse Assay, Injection, Isolation, Affinity Magnetic Separation

    Tumor specific survival after chemotherapeutic treatment of NSG PDX mice bearing four different bladder cancer xenografts Kaplan-Meier survival curves comparing different treatments (N ≥ 8) of A) BL0269, B) BL0293 C) BL0440 and D) BL0645. Black line = Vehicle (D5W IV Q7Dx3), blue line = cisplatin (2 mg/kg IV Q7Dx3), red line = gemcitabine (150 mg/kg IP Q7Dx4), green line = G/C combination chemotherapy (dashed lines represent treatment days).

    Journal: Molecular cancer therapeutics

    Article Title: Microdose-induced Drug-DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice

    doi: 10.1158/1535-7163.MCT-16-0381

    Figure Lengend Snippet: Tumor specific survival after chemotherapeutic treatment of NSG PDX mice bearing four different bladder cancer xenografts Kaplan-Meier survival curves comparing different treatments (N ≥ 8) of A) BL0269, B) BL0293 C) BL0440 and D) BL0645. Black line = Vehicle (D5W IV Q7Dx3), blue line = cisplatin (2 mg/kg IV Q7Dx3), red line = gemcitabine (150 mg/kg IP Q7Dx4), green line = G/C combination chemotherapy (dashed lines represent treatment days).

    Article Snippet: Unlabeled gemcitabine (GEMZAR®) was obtained from Eli Lilly (Indianapolis, IN, USA), and carboplatin (CARBOplatin®, 10 mg/mL) from Hospira (Lake Forest, IL, USA).

    Techniques: Mouse Assay

    Microdose-induced carboplatin- and gemcitabine DNA-adduct levels correlate with PDX drug sensitivity NSG mice were implanted with the indicated PDX tumors 14 to 30 days before microdosing. Animals (N ≥ 4 per group) were dosed via tail vein injection with A and B) 0.375 mg/kg carboplatin, 50,000 dpm/g or C, D and F) 0.092 mg/kg gemcitabine, 1000 dpm/g. Tumors were collected after A and C) 4h or B and D) 24h and 14 C content of isolated tumor DNA was analyzed via AMS. E) Tumor volume ratio of parental PDX model BL0293 (grey line) and resistant model BL0293R (black line). BL0293 was defined as resistant after gemcitabine treatment did not affect tumor growth (8 cycles). Dashed lines represent treatment days. F) Microdose-induced gemcitabine adduct levels at 4h and 24h of BL0293 and BL0293R. One-Way ANOVA with Newman-Keuls post hoc test or Student's t-test was used to measure all p values (* p

    Journal: Molecular cancer therapeutics

    Article Title: Microdose-induced Drug-DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice

    doi: 10.1158/1535-7163.MCT-16-0381

    Figure Lengend Snippet: Microdose-induced carboplatin- and gemcitabine DNA-adduct levels correlate with PDX drug sensitivity NSG mice were implanted with the indicated PDX tumors 14 to 30 days before microdosing. Animals (N ≥ 4 per group) were dosed via tail vein injection with A and B) 0.375 mg/kg carboplatin, 50,000 dpm/g or C, D and F) 0.092 mg/kg gemcitabine, 1000 dpm/g. Tumors were collected after A and C) 4h or B and D) 24h and 14 C content of isolated tumor DNA was analyzed via AMS. E) Tumor volume ratio of parental PDX model BL0293 (grey line) and resistant model BL0293R (black line). BL0293 was defined as resistant after gemcitabine treatment did not affect tumor growth (8 cycles). Dashed lines represent treatment days. F) Microdose-induced gemcitabine adduct levels at 4h and 24h of BL0293 and BL0293R. One-Way ANOVA with Newman-Keuls post hoc test or Student's t-test was used to measure all p values (* p

    Article Snippet: Unlabeled gemcitabine (GEMZAR®) was obtained from Eli Lilly (Indianapolis, IN, USA), and carboplatin (CARBOplatin®, 10 mg/mL) from Hospira (Lake Forest, IL, USA).

    Techniques: Mouse Assay, Injection, Isolation, Affinity Magnetic Separation

    Dose linearity between the microdose and therapeutic dose in PDX xenograft model BL0645 and BL0293 NSG mice were implanted with PDX model BL0645 14 days before microdosing. Animals were dose with A) 37.5 mg/kg carboplatin (50,000 dmp/g, red bar) or 37.5 mg/kg carboplatin (50,000 dpm/g) plus 9.2 mg/kg unlabeled gemcitabine (green bar), B) 9.2 mg/kg gemcitabine (1,000 dpm/g, red bar) or 9.2 mg/kg gemcitabine (1,000 dpm/g) plus 37.5 mg/kg unlabeled carboplatin (green bar). After 24h, DNA was isolated from collected tumor tissue and analyzed via AMS. C) Dose proportionality is shown by plotting microdose and therapeutic dose induced adduct level onto log scale. Student's t-test was used to measure all p values. Presented are means and error bars represent SEM.

    Journal: Molecular cancer therapeutics

    Article Title: Microdose-induced Drug-DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice

    doi: 10.1158/1535-7163.MCT-16-0381

    Figure Lengend Snippet: Dose linearity between the microdose and therapeutic dose in PDX xenograft model BL0645 and BL0293 NSG mice were implanted with PDX model BL0645 14 days before microdosing. Animals were dose with A) 37.5 mg/kg carboplatin (50,000 dmp/g, red bar) or 37.5 mg/kg carboplatin (50,000 dpm/g) plus 9.2 mg/kg unlabeled gemcitabine (green bar), B) 9.2 mg/kg gemcitabine (1,000 dpm/g, red bar) or 9.2 mg/kg gemcitabine (1,000 dpm/g) plus 37.5 mg/kg unlabeled carboplatin (green bar). After 24h, DNA was isolated from collected tumor tissue and analyzed via AMS. C) Dose proportionality is shown by plotting microdose and therapeutic dose induced adduct level onto log scale. Student's t-test was used to measure all p values. Presented are means and error bars represent SEM.

    Article Snippet: Unlabeled gemcitabine (GEMZAR®) was obtained from Eli Lilly (Indianapolis, IN, USA), and carboplatin (CARBOplatin®, 10 mg/mL) from Hospira (Lake Forest, IL, USA).

    Techniques: Mouse Assay, Isolation, Affinity Magnetic Separation

    Effects of compound treatment on mitochondrial mass and cell size. HT29 cells were treated with the indicated drugs for 48 hours. (Aphidicolin; 3.1 µM, Etoposide; 3.9 µM, Gemcitabine; 24 nM, Paclitaxel; 98 nM, VX-680; 195, nM, PD901; 390 nM). A. Images of Hoechst 33452-stained DNA (red) and MitoTracker deep red-FM staining (green) were acquired with a 20x water-immersion objective as described in Methods section. All images are shown at same magnification and intensity scaling. Scale bar = 50 µm. B. MitoTracker deep red images showing identification and segmentation of cell boundaries. C. Scatter plots and histograms of log2-normalized integrated DNA intensity (x axis, upper histogram panels) and integrated cytoplasmic MitoTracker Deep Red FM staining intensity (y axis, right-side histograms) derived from the same wells as shown in part A. D. Variation in cell area and mitochondrial content (integrated MitoTracker deep red intensity) for the same cell populations, normalized as fold change relative to the mean area and intensity of DMSO-treated samples.

    Journal: PLoS ONE

    Article Title: A Simple High-Content Cell Cycle Assay Reveals Frequent Discrepancies between Cell Number and ATP and MTS Proliferation Assays

    doi: 10.1371/journal.pone.0063583

    Figure Lengend Snippet: Effects of compound treatment on mitochondrial mass and cell size. HT29 cells were treated with the indicated drugs for 48 hours. (Aphidicolin; 3.1 µM, Etoposide; 3.9 µM, Gemcitabine; 24 nM, Paclitaxel; 98 nM, VX-680; 195, nM, PD901; 390 nM). A. Images of Hoechst 33452-stained DNA (red) and MitoTracker deep red-FM staining (green) were acquired with a 20x water-immersion objective as described in Methods section. All images are shown at same magnification and intensity scaling. Scale bar = 50 µm. B. MitoTracker deep red images showing identification and segmentation of cell boundaries. C. Scatter plots and histograms of log2-normalized integrated DNA intensity (x axis, upper histogram panels) and integrated cytoplasmic MitoTracker Deep Red FM staining intensity (y axis, right-side histograms) derived from the same wells as shown in part A. D. Variation in cell area and mitochondrial content (integrated MitoTracker deep red intensity) for the same cell populations, normalized as fold change relative to the mean area and intensity of DMSO-treated samples.

    Article Snippet: Compound Treatment Inhibitors were obtained in-house and from commercial vendors: aphidicolin, cisplatin, doxorubicin, etoposide, nocodazole and vinblastine (EMD Chemicals; Philadelphia, PA), gemcitabine (Tocris, Ellisvile, MO), paclitaxel (Life Technologies), 5-fluorouracil (Sigma).

    Techniques: Staining, Derivative Assay

    Cell cycle profiles derived from high-content assay. Cells in the same images used for direct cell counting were classified into five cell cycle bins by integrated DNA intensity. A. Stacked bars show the relative frequencies of the sub-populations at the indicated concentrations. Each bar is the average of two wells. Black circles indicate relative cell number. B. Histograms of integrated DNA intensity derived from the images from individual wells showing the change in cell cycle profile from EC 90 (upper panels) to higher doses of etoposide, gemcitabine and VX-680.

    Journal: PLoS ONE

    Article Title: A Simple High-Content Cell Cycle Assay Reveals Frequent Discrepancies between Cell Number and ATP and MTS Proliferation Assays

    doi: 10.1371/journal.pone.0063583

    Figure Lengend Snippet: Cell cycle profiles derived from high-content assay. Cells in the same images used for direct cell counting were classified into five cell cycle bins by integrated DNA intensity. A. Stacked bars show the relative frequencies of the sub-populations at the indicated concentrations. Each bar is the average of two wells. Black circles indicate relative cell number. B. Histograms of integrated DNA intensity derived from the images from individual wells showing the change in cell cycle profile from EC 90 (upper panels) to higher doses of etoposide, gemcitabine and VX-680.

    Article Snippet: Compound Treatment Inhibitors were obtained in-house and from commercial vendors: aphidicolin, cisplatin, doxorubicin, etoposide, nocodazole and vinblastine (EMD Chemicals; Philadelphia, PA), gemcitabine (Tocris, Ellisvile, MO), paclitaxel (Life Technologies), 5-fluorouracil (Sigma).

    Techniques: Derivative Assay, Cell Counting

    Drug-induced increases in mitochondrial mass correlate with increases in per-cell ATP and MTS assay signal. A. Correlation between ATP/cell (RLU/cell number) vs mean per-cell integrated MitoTracker intensity for each point of the dose-response curves. Each point is the mean of replicate wells. Colors indicate relative concentrations in 2-fold dilutions from highest (red) to lowest (blue). Points are connected in order of concentration. B, C Upper panels show fold change in mean per-cell integrated MitoTracker staining intensity as a function of concentration. Lower panels show dose-response curves for the total mitochondrial mass, (cell number multiplied by mean per-cell MitoTracker intensity) (purple) overlaid with the ATP assay data (blue). B. HT29 cells treated with the indicated compounds. C. Different cell lines as indicated treated with gemcitabine.

    Journal: PLoS ONE

    Article Title: A Simple High-Content Cell Cycle Assay Reveals Frequent Discrepancies between Cell Number and ATP and MTS Proliferation Assays

    doi: 10.1371/journal.pone.0063583

    Figure Lengend Snippet: Drug-induced increases in mitochondrial mass correlate with increases in per-cell ATP and MTS assay signal. A. Correlation between ATP/cell (RLU/cell number) vs mean per-cell integrated MitoTracker intensity for each point of the dose-response curves. Each point is the mean of replicate wells. Colors indicate relative concentrations in 2-fold dilutions from highest (red) to lowest (blue). Points are connected in order of concentration. B, C Upper panels show fold change in mean per-cell integrated MitoTracker staining intensity as a function of concentration. Lower panels show dose-response curves for the total mitochondrial mass, (cell number multiplied by mean per-cell MitoTracker intensity) (purple) overlaid with the ATP assay data (blue). B. HT29 cells treated with the indicated compounds. C. Different cell lines as indicated treated with gemcitabine.

    Article Snippet: Compound Treatment Inhibitors were obtained in-house and from commercial vendors: aphidicolin, cisplatin, doxorubicin, etoposide, nocodazole and vinblastine (EMD Chemicals; Philadelphia, PA), gemcitabine (Tocris, Ellisvile, MO), paclitaxel (Life Technologies), 5-fluorouracil (Sigma).

    Techniques: MTS Assay, Concentration Assay, Staining, ATP Assay

    Effects of drug treatment on mitochondrial function. Basal oxygen consumption rate (OCR) determined for cells treated with the indicated compounds (etoposide, 10 µM; gemcitabine 0.1 µM; paclitaxel 0.01 µM; PD901 1 µM, VX-680 0.2 µM) were normalized for cell number. Per-cell OCR is compared with normalized ATP-generated RLU ( A ) and mitochondrial mass ( B ). Cells analyzed for mitochondrial mass by MitoTracker Deep Red staining were also stained with the mitochondrial membrane potential-sensitive dye TMRE, and the mean integrated intensities compared ( C ). All data were normalized as a ratio of the mean DMSO-treated values and are the mean of four replicate wells, error bars show standard deviation.

    Journal: PLoS ONE

    Article Title: A Simple High-Content Cell Cycle Assay Reveals Frequent Discrepancies between Cell Number and ATP and MTS Proliferation Assays

    doi: 10.1371/journal.pone.0063583

    Figure Lengend Snippet: Effects of drug treatment on mitochondrial function. Basal oxygen consumption rate (OCR) determined for cells treated with the indicated compounds (etoposide, 10 µM; gemcitabine 0.1 µM; paclitaxel 0.01 µM; PD901 1 µM, VX-680 0.2 µM) were normalized for cell number. Per-cell OCR is compared with normalized ATP-generated RLU ( A ) and mitochondrial mass ( B ). Cells analyzed for mitochondrial mass by MitoTracker Deep Red staining were also stained with the mitochondrial membrane potential-sensitive dye TMRE, and the mean integrated intensities compared ( C ). All data were normalized as a ratio of the mean DMSO-treated values and are the mean of four replicate wells, error bars show standard deviation.

    Article Snippet: Compound Treatment Inhibitors were obtained in-house and from commercial vendors: aphidicolin, cisplatin, doxorubicin, etoposide, nocodazole and vinblastine (EMD Chemicals; Philadelphia, PA), gemcitabine (Tocris, Ellisvile, MO), paclitaxel (Life Technologies), 5-fluorouracil (Sigma).

    Techniques: Generated, Staining, Standard Deviation

    Time-dependence of discrepancies between cell number and ATP assay. A. EC 50 and E max values HT29 and A375 cells treated with etoposide or gemcitabine for the indicated periods of time were assayed by ATP and high-content assays as described. ND, not determined – no valid curve fit was possible by the standard acceptance criteria described in methods . Assay dose-response curves ( B,C ) and cell cycle profiles ( D,E ) for A375 and HT29 cells treated with etoposide ( B,D ) and gemcitabine ( C,E ).

    Journal: PLoS ONE

    Article Title: A Simple High-Content Cell Cycle Assay Reveals Frequent Discrepancies between Cell Number and ATP and MTS Proliferation Assays

    doi: 10.1371/journal.pone.0063583

    Figure Lengend Snippet: Time-dependence of discrepancies between cell number and ATP assay. A. EC 50 and E max values HT29 and A375 cells treated with etoposide or gemcitabine for the indicated periods of time were assayed by ATP and high-content assays as described. ND, not determined – no valid curve fit was possible by the standard acceptance criteria described in methods . Assay dose-response curves ( B,C ) and cell cycle profiles ( D,E ) for A375 and HT29 cells treated with etoposide ( B,D ) and gemcitabine ( C,E ).

    Article Snippet: Compound Treatment Inhibitors were obtained in-house and from commercial vendors: aphidicolin, cisplatin, doxorubicin, etoposide, nocodazole and vinblastine (EMD Chemicals; Philadelphia, PA), gemcitabine (Tocris, Ellisvile, MO), paclitaxel (Life Technologies), 5-fluorouracil (Sigma).

    Techniques: ATP Assay

    CM03 treatment reduces tumor volume in a MIA PaCa-2 xenograft model of PDAC. (a) Plot showing the tumor volume of MIA PaCa-2 xenografts treated with CM03, MM41, gemcitabine, or saline (control) over 62 days. There are eight CD-1 mice per condition and dosing for all cohorts was stopped on day 28, shown by the red arrow. Standard error of the mean (SEM) is indicated for all growth curves for each tumor volume. * p

    Journal: Journal of Medicinal Chemistry

    Article Title: Targeting Multiple Effector Pathways in Pancreatic Ductal Adenocarcinoma with a G-Quadruplex-Binding Small Molecule

    doi: 10.1021/acs.jmedchem.7b01781

    Figure Lengend Snippet: CM03 treatment reduces tumor volume in a MIA PaCa-2 xenograft model of PDAC. (a) Plot showing the tumor volume of MIA PaCa-2 xenografts treated with CM03, MM41, gemcitabine, or saline (control) over 62 days. There are eight CD-1 mice per condition and dosing for all cohorts was stopped on day 28, shown by the red arrow. Standard error of the mean (SEM) is indicated for all growth curves for each tumor volume. * p

    Article Snippet: Next day, cells were treated with 400 nM CM03 for 6 and 24 h. For gemcitabine treatment, cells were treated for 6 and 24 h with DMSO or 30 nM, 100 nM, 300 nM, 1 μM, 3 μM, and 10 μM gemcitabine-HCL for PANC-1 cells and 30 nM, 300 nM, and 3 μM gemcitabine-HCl for MIA PaCa-2 cells.

    Techniques: Mouse Assay

    Reduced miR-30a expression correlates with tumor progression and lower patient survival rate in pancreatic cancers. a MiR-30a expression in tumor and adjacent normal pancreatic tissues was determined using qRT-PCR (88 pancreatic cancer samples and 88 normal pancreatic tissues). Error bars, ±SEM. b SNAI1 gene expression in tumor and adjacent normal pancreatic tissues was determined using qRT-PCR (88 pancreatic cancer samples and 88 normal pancreatic tissues, as shown in a ). Error bars, ±SEM. c Representative miR-30a expression in tumor and normal pancreatic tissues was determined using qRT-PCR (12 pancreatic cancer samples and 12 normal pancreatic tissues). Error bars, ±SEM. d Correlation study of miR-30a and SNAI1 in pancreatic carcinoma. Statistical analyses were performed with the χ 2 test. R , Pearson correlation coefficient. e Correlation study between miR-30a level and gemcitabine response in pancreatic carcinoma with the χ 2 test. R , Pearson correlation coefficient. f Association between miR-30a expression level and overall survival rate analyzed by the Kaplan–Meier method. Patients were split into high and low expression groups based on the median expression of the miR-30a. g Evaluation of tumor growth for xenograft mouse models of pancreatic cancer. Mice were inoculated subcutaneously in the right flank with 0.1 ml matrigel containing 2 × 10 6 cells. Representative images of tumor were captured at the end of 3 weeks. n = 5 per group. h Gemcitabine response in miR-Con or miR-30a xenograft mice. Results are represented by the tumor volume measured at each time point normalized to day 0. Data are presented as means ± SEM ( n = 5 per group). i MiR-30a xenografts are sensitive to gemcitabine in vivo. Results are represented by tumor inhibition ratio, calculated as follows: tumor volume at each time point normalized to day 0 for gemcitabine treated mice, corrected for that of vehicle group mice. * P

    Journal: Cell Death & Disease

    Article Title: MiR-30a regulates cancer cell response to chemotherapy through SNAI1/IRS1/AKT pathway

    doi: 10.1038/s41419-019-1326-6

    Figure Lengend Snippet: Reduced miR-30a expression correlates with tumor progression and lower patient survival rate in pancreatic cancers. a MiR-30a expression in tumor and adjacent normal pancreatic tissues was determined using qRT-PCR (88 pancreatic cancer samples and 88 normal pancreatic tissues). Error bars, ±SEM. b SNAI1 gene expression in tumor and adjacent normal pancreatic tissues was determined using qRT-PCR (88 pancreatic cancer samples and 88 normal pancreatic tissues, as shown in a ). Error bars, ±SEM. c Representative miR-30a expression in tumor and normal pancreatic tissues was determined using qRT-PCR (12 pancreatic cancer samples and 12 normal pancreatic tissues). Error bars, ±SEM. d Correlation study of miR-30a and SNAI1 in pancreatic carcinoma. Statistical analyses were performed with the χ 2 test. R , Pearson correlation coefficient. e Correlation study between miR-30a level and gemcitabine response in pancreatic carcinoma with the χ 2 test. R , Pearson correlation coefficient. f Association between miR-30a expression level and overall survival rate analyzed by the Kaplan–Meier method. Patients were split into high and low expression groups based on the median expression of the miR-30a. g Evaluation of tumor growth for xenograft mouse models of pancreatic cancer. Mice were inoculated subcutaneously in the right flank with 0.1 ml matrigel containing 2 × 10 6 cells. Representative images of tumor were captured at the end of 3 weeks. n = 5 per group. h Gemcitabine response in miR-Con or miR-30a xenograft mice. Results are represented by the tumor volume measured at each time point normalized to day 0. Data are presented as means ± SEM ( n = 5 per group). i MiR-30a xenografts are sensitive to gemcitabine in vivo. Results are represented by tumor inhibition ratio, calculated as follows: tumor volume at each time point normalized to day 0 for gemcitabine treated mice, corrected for that of vehicle group mice. * P

    Article Snippet: The gemcitabine (Gemzar) drug was purchased from Eli Lilly and Company (Indianapolis, Indiana, USA).

    Techniques: Expressing, Quantitative RT-PCR, Mouse Assay, In Vivo, Inhibition

    Working model of miRNAs functions in chemoresistance. MiR-30a regulates cancer cell response to chemotherapy through SNAI1/IRS1/ERK/AKT pathway. On the other hand, miR-30a is a downstream target gene of AKT-FOXO30a that forms a feedback loop. In addition, it is highly possible that other miRNAs identified by miRNA screen may also be involved in gemcitabine response and are worth exploring further

    Journal: Cell Death & Disease

    Article Title: MiR-30a regulates cancer cell response to chemotherapy through SNAI1/IRS1/AKT pathway

    doi: 10.1038/s41419-019-1326-6

    Figure Lengend Snippet: Working model of miRNAs functions in chemoresistance. MiR-30a regulates cancer cell response to chemotherapy through SNAI1/IRS1/ERK/AKT pathway. On the other hand, miR-30a is a downstream target gene of AKT-FOXO30a that forms a feedback loop. In addition, it is highly possible that other miRNAs identified by miRNA screen may also be involved in gemcitabine response and are worth exploring further

    Article Snippet: The gemcitabine (Gemzar) drug was purchased from Eli Lilly and Company (Indianapolis, Indiana, USA).

    Techniques:

    Deep sequencing of small RNAs associated with gemcitabine response. a , b Drug-resistance cell line was established as described in the Materials and methods. Gemcitabine sensitivity of both SW1990-R cells and its parental cells ( a ) were tested by MTS assay and the IC50 values were calculated ( b ). * P

    Journal: Cell Death & Disease

    Article Title: MiR-30a regulates cancer cell response to chemotherapy through SNAI1/IRS1/AKT pathway

    doi: 10.1038/s41419-019-1326-6

    Figure Lengend Snippet: Deep sequencing of small RNAs associated with gemcitabine response. a , b Drug-resistance cell line was established as described in the Materials and methods. Gemcitabine sensitivity of both SW1990-R cells and its parental cells ( a ) were tested by MTS assay and the IC50 values were calculated ( b ). * P

    Article Snippet: The gemcitabine (Gemzar) drug was purchased from Eli Lilly and Company (Indianapolis, Indiana, USA).

    Techniques: Sequencing, MTS Assay

    MiR-30a functions as tumor suppressor partly through SNAI1/IRS1/AKT/ERK pathway. a The effect of miR-30a modulation (miR-con, miR-30a and miR-30a inhibitor) on IRS1 and SNAI1 protein expression by western blot analysis in SW1990 cells. b MiR-30a targets SNAI1 directly. Representative seed sequences for miR-30a on the SNAI1 3′UTR was shown (left). 293T cells were transiently transfected with pmirGlo plasmids encoding wild-type or mutated 3′UTR sequences of SNAI1, and oligos. Luciferase activities were then measured 24 h after transfection (right). Firefly luciferase was normalized to Renilla luciferase. The data are represented as mean ± SEM ( n = 3). c – e Knockdown of SNAI1 by transfection of two different SNAI1 siRNAs (si-SNAI1–1, si -SNAI1–2) in SW1990 cells. Cell growth ( c ) and gemcitabine sensitivity ( d ) were tested by MTS assay. Downstream proteins of SNAI1 were examined by western blot ( e ). * P

    Journal: Cell Death & Disease

    Article Title: MiR-30a regulates cancer cell response to chemotherapy through SNAI1/IRS1/AKT pathway

    doi: 10.1038/s41419-019-1326-6

    Figure Lengend Snippet: MiR-30a functions as tumor suppressor partly through SNAI1/IRS1/AKT/ERK pathway. a The effect of miR-30a modulation (miR-con, miR-30a and miR-30a inhibitor) on IRS1 and SNAI1 protein expression by western blot analysis in SW1990 cells. b MiR-30a targets SNAI1 directly. Representative seed sequences for miR-30a on the SNAI1 3′UTR was shown (left). 293T cells were transiently transfected with pmirGlo plasmids encoding wild-type or mutated 3′UTR sequences of SNAI1, and oligos. Luciferase activities were then measured 24 h after transfection (right). Firefly luciferase was normalized to Renilla luciferase. The data are represented as mean ± SEM ( n = 3). c – e Knockdown of SNAI1 by transfection of two different SNAI1 siRNAs (si-SNAI1–1, si -SNAI1–2) in SW1990 cells. Cell growth ( c ) and gemcitabine sensitivity ( d ) were tested by MTS assay. Downstream proteins of SNAI1 were examined by western blot ( e ). * P

    Article Snippet: The gemcitabine (Gemzar) drug was purchased from Eli Lilly and Company (Indianapolis, Indiana, USA).

    Techniques: Expressing, Western Blot, Transfection, Luciferase, MTS Assay

    MiR-30a suppresses cell proliferation and enhances cell sensitivity to gemcitabine. a , b SW1990 cells were transfected with miR-30a precursor (miR-30a) or scramble control lentivirus (miR-Con). MiR-30a level was confirmed by qRT-PCR ( a ). Gemcitabine sensitivity was determined by MTS assays ( b ). * P

    Journal: Cell Death & Disease

    Article Title: MiR-30a regulates cancer cell response to chemotherapy through SNAI1/IRS1/AKT pathway

    doi: 10.1038/s41419-019-1326-6

    Figure Lengend Snippet: MiR-30a suppresses cell proliferation and enhances cell sensitivity to gemcitabine. a , b SW1990 cells were transfected with miR-30a precursor (miR-30a) or scramble control lentivirus (miR-Con). MiR-30a level was confirmed by qRT-PCR ( a ). Gemcitabine sensitivity was determined by MTS assays ( b ). * P

    Article Snippet: The gemcitabine (Gemzar) drug was purchased from Eli Lilly and Company (Indianapolis, Indiana, USA).

    Techniques: Transfection, Quantitative RT-PCR

    Concentration-dependent cytotoxic effect of gemcitabine or cisplatin. a : KMBC (blue circles) and HuCCT1 (purple squares) cells and b : haploid BAP1 knockout (HAP1 BAP1 KO) ( green circles ) or parental haploid HAP1 cells (WT) ( orange squares ) were plated in 384-well plates (1,000 cells/well), and incubated with varying concentrations of gemcitabine or cisplatin. Cell viability was assessed after 72 h using Cell Titer GloR 2.0 assay. Data represents the average percent cell viability plotted against concentration of drug in nM from 4 replicates for each condition. The table indicates the inhibitory concentration at 50% effect (IC50) values for each drug for each of the cell lines

    Journal: Molecular Cancer

    Article Title: BAP1 dependent expression of long non-coding RNA NEAT-1 contributes to sensitivity to gemcitabine in cholangiocarcinoma

    doi: 10.1186/s12943-017-0587-x

    Figure Lengend Snippet: Concentration-dependent cytotoxic effect of gemcitabine or cisplatin. a : KMBC (blue circles) and HuCCT1 (purple squares) cells and b : haploid BAP1 knockout (HAP1 BAP1 KO) ( green circles ) or parental haploid HAP1 cells (WT) ( orange squares ) were plated in 384-well plates (1,000 cells/well), and incubated with varying concentrations of gemcitabine or cisplatin. Cell viability was assessed after 72 h using Cell Titer GloR 2.0 assay. Data represents the average percent cell viability plotted against concentration of drug in nM from 4 replicates for each condition. The table indicates the inhibitory concentration at 50% effect (IC50) values for each drug for each of the cell lines

    Article Snippet: Gemcitabine was obtained from Selleckchem (Houston,TX), cisplatin (Sigma-Aldrich, St. Louis, MO), olaparib and GSK126 were obtained from Selleckchem (Houston, TX) and Cayman chemical (Ann Arbor, MI) respectively; trichostatin A (Santa Cruz Biotechnology, Santa Cruz, CA), and b-AP15 (VLX1500) were provided by Dr. Asher Chanan-Khan.

    Techniques: Concentration Assay, Knock-Out, Incubation

    Synergistic interactions between candidate agents with gemcitabine. a : Cytotoxicity to drugs was assessed in KMBC (blue circles) and HuCCT1 (purple squares) cells incubated with gemcitabine (Gem) in combination with trichostatin A (TSA), b-AP15, olaparib, or GSK126 in a fixed ratio of concentrations, based on the IC50 of each drug. Potential interactions were evaluated using the median effects analysis of Chou and Talalay, and the combination index (CI) derived, with a CI

    Journal: Molecular Cancer

    Article Title: BAP1 dependent expression of long non-coding RNA NEAT-1 contributes to sensitivity to gemcitabine in cholangiocarcinoma

    doi: 10.1186/s12943-017-0587-x

    Figure Lengend Snippet: Synergistic interactions between candidate agents with gemcitabine. a : Cytotoxicity to drugs was assessed in KMBC (blue circles) and HuCCT1 (purple squares) cells incubated with gemcitabine (Gem) in combination with trichostatin A (TSA), b-AP15, olaparib, or GSK126 in a fixed ratio of concentrations, based on the IC50 of each drug. Potential interactions were evaluated using the median effects analysis of Chou and Talalay, and the combination index (CI) derived, with a CI

    Article Snippet: Gemcitabine was obtained from Selleckchem (Houston,TX), cisplatin (Sigma-Aldrich, St. Louis, MO), olaparib and GSK126 were obtained from Selleckchem (Houston, TX) and Cayman chemical (Ann Arbor, MI) respectively; trichostatin A (Santa Cruz Biotechnology, Santa Cruz, CA), and b-AP15 (VLX1500) were provided by Dr. Asher Chanan-Khan.

    Techniques: Incubation, Derivative Assay

    HPA1 inhibitor attenuates gemcitabine-induced invasiveness of PC cells in vitro (A) In vitro cell invasion of PANC-1 and SW1990 cells treated with gemcitabine (10μM, 24 hours) alone or in combination with OGT2115 (1 μM), BAY 11-7082 (10 μM) or erlotinib (5 μM). Invaded cells were stained with 0.1% crystal violet and examined by light microscopy (B) . Invasion ability of (B) PANC-1 and (C) SW1990 cells was determined by counting the cells invaded to the lower chamber. Scale bar, 100 μm. *p

    Journal: Oncotarget

    Article Title: Gemcitabine-induced heparanase promotes aggressiveness of pancreatic cancer cells via activating EGFR signaling

    doi: 10.18632/oncotarget.16911

    Figure Lengend Snippet: HPA1 inhibitor attenuates gemcitabine-induced invasiveness of PC cells in vitro (A) In vitro cell invasion of PANC-1 and SW1990 cells treated with gemcitabine (10μM, 24 hours) alone or in combination with OGT2115 (1 μM), BAY 11-7082 (10 μM) or erlotinib (5 μM). Invaded cells were stained with 0.1% crystal violet and examined by light microscopy (B) . Invasion ability of (B) PANC-1 and (C) SW1990 cells was determined by counting the cells invaded to the lower chamber. Scale bar, 100 μm. *p

    Article Snippet: Antibodies and reagents Gemcitabine, LY294002, PD98059, SP600125, SB203580 and erlotinib were purchased from Selleck Chemicals (Houston, TX).

    Techniques: In Vitro, Staining, Light Microscopy

    The involvement of NF-κB signaling in gemcitabine-induced HPA1 expression PANC-1 cells and SW1990 cells were pretreated with BAY 11-7082 (10 μM), LY294002 (5 μM), PD98059 (5 μM), SP600125 (10 μM), SB203580 (10 μM) or erlotinib (5 μM) for 2 h and then treated 10 μM gemcitabine for 24 h. (A) mRNA levels of HPA1 were detected by qRT-PCR. *p

    Journal: Oncotarget

    Article Title: Gemcitabine-induced heparanase promotes aggressiveness of pancreatic cancer cells via activating EGFR signaling

    doi: 10.18632/oncotarget.16911

    Figure Lengend Snippet: The involvement of NF-κB signaling in gemcitabine-induced HPA1 expression PANC-1 cells and SW1990 cells were pretreated with BAY 11-7082 (10 μM), LY294002 (5 μM), PD98059 (5 μM), SP600125 (10 μM), SB203580 (10 μM) or erlotinib (5 μM) for 2 h and then treated 10 μM gemcitabine for 24 h. (A) mRNA levels of HPA1 were detected by qRT-PCR. *p

    Article Snippet: Antibodies and reagents Gemcitabine, LY294002, PD98059, SP600125, SB203580 and erlotinib were purchased from Selleck Chemicals (Houston, TX).

    Techniques: Expressing, Quantitative RT-PCR

    Gemcitabine induces the expression of HPA1 in PC cells in vitro and in vivo (A) The mRNA expression of HPA1 was determined using qRT-PCR in SW1990 ( left panel ) and PANC-1 ( right panel ) cells with or without 10 μM gemcitabine treatment for the indicated times. Results are representative of three independent experiments. (B) Western blot analysis was used to determine protein abundance of HPA1 after treatment with 10 μM gemcitabine at the indicated time points. (C) BALB/c nude mice bearing SW1990 xenografts were administered a single dose of vehicle (PBS) or gemcitabine (GEM, 50 mg/kg) for either 24 or 48 h. Tumor tissues were obtained and HPA1 mRNA levels were analyzed by qRT-PCR. (D) Immunohistochemistry was applied to detect the expression of HPA1 in xenografts following treatment with gemcitabine. Representative images are shown with a scale bar of 20 μm. *p

    Journal: Oncotarget

    Article Title: Gemcitabine-induced heparanase promotes aggressiveness of pancreatic cancer cells via activating EGFR signaling

    doi: 10.18632/oncotarget.16911

    Figure Lengend Snippet: Gemcitabine induces the expression of HPA1 in PC cells in vitro and in vivo (A) The mRNA expression of HPA1 was determined using qRT-PCR in SW1990 ( left panel ) and PANC-1 ( right panel ) cells with or without 10 μM gemcitabine treatment for the indicated times. Results are representative of three independent experiments. (B) Western blot analysis was used to determine protein abundance of HPA1 after treatment with 10 μM gemcitabine at the indicated time points. (C) BALB/c nude mice bearing SW1990 xenografts were administered a single dose of vehicle (PBS) or gemcitabine (GEM, 50 mg/kg) for either 24 or 48 h. Tumor tissues were obtained and HPA1 mRNA levels were analyzed by qRT-PCR. (D) Immunohistochemistry was applied to detect the expression of HPA1 in xenografts following treatment with gemcitabine. Representative images are shown with a scale bar of 20 μm. *p

    Article Snippet: Antibodies and reagents Gemcitabine, LY294002, PD98059, SP600125, SB203580 and erlotinib were purchased from Selleck Chemicals (Houston, TX).

    Techniques: Expressing, In Vitro, In Vivo, Quantitative RT-PCR, Western Blot, Mouse Assay, Immunohistochemistry

    Cells with ST6Gal-I knockdown exhibit reduced survival upon exposure to gemcitabine. A and B , ST6Gal-I KD in MiaPaCa-2 ( A ) and BxPC-3 ( B ) cells as depicted by immunoblotting. EV is the control. MiaPaCa-2 ( C ) and BxPC-3 ( D ) cells have reduced ST6Gal-I activity as indicated by decreased surface α2–6 sialylation. α2–6 sialylation was measured by staining cells with the SNA lectin followed by flow cytometry. E and F , representative images of MiaPaCa-2 and BxPC-3 cells showing that gemcitabine ( Gem )-treated KD cells have reduced colony-forming potential compared with gemcitabine-treated EV cells. G and H , MiaPaCa-2 and BxPC-3 KD cells display a significantly reduced survival fraction post-gemcitabine treatment compared with the control EV populations. Graphs depict results from three independent experiments with each independent experiment performed in triplicate. Error bars represent S.E. * denotes p

    Journal: The Journal of Biological Chemistry

    Article Title: ST6Gal-I sialyltransferase promotes chemoresistance in pancreatic ductal adenocarcinoma by abrogating gemcitabine-mediated DNA damage

    doi: 10.1074/jbc.M117.808584

    Figure Lengend Snippet: Cells with ST6Gal-I knockdown exhibit reduced survival upon exposure to gemcitabine. A and B , ST6Gal-I KD in MiaPaCa-2 ( A ) and BxPC-3 ( B ) cells as depicted by immunoblotting. EV is the control. MiaPaCa-2 ( C ) and BxPC-3 ( D ) cells have reduced ST6Gal-I activity as indicated by decreased surface α2–6 sialylation. α2–6 sialylation was measured by staining cells with the SNA lectin followed by flow cytometry. E and F , representative images of MiaPaCa-2 and BxPC-3 cells showing that gemcitabine ( Gem )-treated KD cells have reduced colony-forming potential compared with gemcitabine-treated EV cells. G and H , MiaPaCa-2 and BxPC-3 KD cells display a significantly reduced survival fraction post-gemcitabine treatment compared with the control EV populations. Graphs depict results from three independent experiments with each independent experiment performed in triplicate. Error bars represent S.E. * denotes p

    Article Snippet: For acute gemcitabine treatments (24–72 h), cells were serum-starved for 4 h prior to treatment with 200 n m gemcitabine (Selleck Chemicals, catalog number S1149) for MiaPaCa-2 and Suit2-013 cells, whereas 400 n m gemcitabine was used for BxPC-3 cells (as they appear to be more inherently resistant).

    Techniques: Activity Assay, Staining, Flow Cytometry, Cytometry

    Gemcitabine-treated ST6Gal-I KD cells have increased DNA damage as measured by comet assay. Representative images depict increased tail lengths in MiaPaCa-2 KD ( A ) and BxPC-3 KD ( B ) cells. MiaPaCa-2 KD ( C ) and BxPC-3 KD ( D ) cells treated with gemcitabine ( Gem ) had a significantly increased tail moment compared with gemcitabine-treated EV cells. Graphs depict results from three independent experiments. Error bars represent S.E. * denotes p

    Journal: The Journal of Biological Chemistry

    Article Title: ST6Gal-I sialyltransferase promotes chemoresistance in pancreatic ductal adenocarcinoma by abrogating gemcitabine-mediated DNA damage

    doi: 10.1074/jbc.M117.808584

    Figure Lengend Snippet: Gemcitabine-treated ST6Gal-I KD cells have increased DNA damage as measured by comet assay. Representative images depict increased tail lengths in MiaPaCa-2 KD ( A ) and BxPC-3 KD ( B ) cells. MiaPaCa-2 KD ( C ) and BxPC-3 KD ( D ) cells treated with gemcitabine ( Gem ) had a significantly increased tail moment compared with gemcitabine-treated EV cells. Graphs depict results from three independent experiments. Error bars represent S.E. * denotes p

    Article Snippet: For acute gemcitabine treatments (24–72 h), cells were serum-starved for 4 h prior to treatment with 200 n m gemcitabine (Selleck Chemicals, catalog number S1149) for MiaPaCa-2 and Suit2-013 cells, whereas 400 n m gemcitabine was used for BxPC-3 cells (as they appear to be more inherently resistant).

    Techniques: Single Cell Gel Electrophoresis

    ST6Gal-I knockdown increases the GSR. MiaPaCa-2 KD ( A ) and BxPC-3 KD ( B ) cells treated with gemcitabine ( Gem ) have a significantly increased GSR compared with gemcitabine-treated EV cells. Graphs depict results from three independent experiments with each experiment performed in triplicate. Error bars represent S.E. * denotes p

    Journal: The Journal of Biological Chemistry

    Article Title: ST6Gal-I sialyltransferase promotes chemoresistance in pancreatic ductal adenocarcinoma by abrogating gemcitabine-mediated DNA damage

    doi: 10.1074/jbc.M117.808584

    Figure Lengend Snippet: ST6Gal-I knockdown increases the GSR. MiaPaCa-2 KD ( A ) and BxPC-3 KD ( B ) cells treated with gemcitabine ( Gem ) have a significantly increased GSR compared with gemcitabine-treated EV cells. Graphs depict results from three independent experiments with each experiment performed in triplicate. Error bars represent S.E. * denotes p

    Article Snippet: For acute gemcitabine treatments (24–72 h), cells were serum-starved for 4 h prior to treatment with 200 n m gemcitabine (Selleck Chemicals, catalog number S1149) for MiaPaCa-2 and Suit2-013 cells, whereas 400 n m gemcitabine was used for BxPC-3 cells (as they appear to be more inherently resistant).

    Techniques:

    Removal of surface sialic acids reverses the protective effect of ST6Gal-I on gemcitabine-induced cell death. A , mean fluorescence intensity ( MFI ) values for cells stained with either SNA or MAA lectin. Lectin staining was conducted on UT cells or cells incubated with A. ureafaciens neuraminidase ( neura ) for 30 min. B , EV and KD cells were treated with or without gemcitabine ( Gem ) for 24 h and monitored for cleavage (activation) of caspase 3. C , cells were pretreated with neuraminidase for 30 min and then incubated with gemcitabine for 24 h. Immunoblots of cleaved caspase 3 ( cl. casp 3 ) show that neuraminidase treatment sensitized EV, but not KD, cells to gemcitabine. D , cells were incubated with anti-TNFR1 function–blocking antibody and gemcitabine for 24 h. The TNFR1-blocking antibody potentiated gemcitabine-induced cell death and eliminated differences in EV and KD apoptotic responses. inhib , inhibitor.

    Journal: The Journal of Biological Chemistry

    Article Title: ST6Gal-I sialyltransferase promotes chemoresistance in pancreatic ductal adenocarcinoma by abrogating gemcitabine-mediated DNA damage

    doi: 10.1074/jbc.M117.808584

    Figure Lengend Snippet: Removal of surface sialic acids reverses the protective effect of ST6Gal-I on gemcitabine-induced cell death. A , mean fluorescence intensity ( MFI ) values for cells stained with either SNA or MAA lectin. Lectin staining was conducted on UT cells or cells incubated with A. ureafaciens neuraminidase ( neura ) for 30 min. B , EV and KD cells were treated with or without gemcitabine ( Gem ) for 24 h and monitored for cleavage (activation) of caspase 3. C , cells were pretreated with neuraminidase for 30 min and then incubated with gemcitabine for 24 h. Immunoblots of cleaved caspase 3 ( cl. casp 3 ) show that neuraminidase treatment sensitized EV, but not KD, cells to gemcitabine. D , cells were incubated with anti-TNFR1 function–blocking antibody and gemcitabine for 24 h. The TNFR1-blocking antibody potentiated gemcitabine-induced cell death and eliminated differences in EV and KD apoptotic responses. inhib , inhibitor.

    Article Snippet: For acute gemcitabine treatments (24–72 h), cells were serum-starved for 4 h prior to treatment with 200 n m gemcitabine (Selleck Chemicals, catalog number S1149) for MiaPaCa-2 and Suit2-013 cells, whereas 400 n m gemcitabine was used for BxPC-3 cells (as they appear to be more inherently resistant).

    Techniques: Fluorescence, Staining, Incubation, Activation Assay, Western Blot, Blocking Assay, Inhibition

    A metastatic, chemoresistant Suit-2 subclone with up-regulated ST6Gal-I can be sensitized to gemcitabine by ST6Gal-I knockdown. A , Suit-2 cells with no detectable ST6Gal-I compared with three Suit2-derived metastatic subclones, S2-CP9, S2-LM7AA, and S2-013. All of the metastatic derivatives have increased ST6Gal-I expression as measured by immunoblotting. B , ST6Gal-I was knocked down in the S2-013 line, and reduced expression was verified by immunoblotting. C , reduction in SNA staining in KD cells, indicative of reduced surface α2–6 sialylation. D , S2-013 KD cells have increased gemcitabine ( Gem )-induced cell death relative to EV cells as indicated by increased expression of cleaved caspase 3. S2-013 KD cells have decreased clonogenic potential ( E ) and significantly reduced survival fraction ( F ). The graph depicts results from three independent experiments with each experiment performed in triplicate. Error bars represent S.E. * denotes p

    Journal: The Journal of Biological Chemistry

    Article Title: ST6Gal-I sialyltransferase promotes chemoresistance in pancreatic ductal adenocarcinoma by abrogating gemcitabine-mediated DNA damage

    doi: 10.1074/jbc.M117.808584

    Figure Lengend Snippet: A metastatic, chemoresistant Suit-2 subclone with up-regulated ST6Gal-I can be sensitized to gemcitabine by ST6Gal-I knockdown. A , Suit-2 cells with no detectable ST6Gal-I compared with three Suit2-derived metastatic subclones, S2-CP9, S2-LM7AA, and S2-013. All of the metastatic derivatives have increased ST6Gal-I expression as measured by immunoblotting. B , ST6Gal-I was knocked down in the S2-013 line, and reduced expression was verified by immunoblotting. C , reduction in SNA staining in KD cells, indicative of reduced surface α2–6 sialylation. D , S2-013 KD cells have increased gemcitabine ( Gem )-induced cell death relative to EV cells as indicated by increased expression of cleaved caspase 3. S2-013 KD cells have decreased clonogenic potential ( E ) and significantly reduced survival fraction ( F ). The graph depicts results from three independent experiments with each experiment performed in triplicate. Error bars represent S.E. * denotes p

    Article Snippet: For acute gemcitabine treatments (24–72 h), cells were serum-starved for 4 h prior to treatment with 200 n m gemcitabine (Selleck Chemicals, catalog number S1149) for MiaPaCa-2 and Suit2-013 cells, whereas 400 n m gemcitabine was used for BxPC-3 cells (as they appear to be more inherently resistant).

    Techniques: Derivative Assay, Expressing, Staining

    S2-013 KD cells exhibit enhanced gemcitabine-induced DNA damage. A , representative images of gemcitabine ( Gem )-treated S2-013 cells evaluated by comet assay. B , gemcitabine-treated S2-013 KD cells depict significantly increased tail moment compared with gemcitabine-treated EV cells. C , representative images of S2-013 cells stained for γH2AX foci. D , quantification of γH2AX foci in Suit2-013 EV and KD cells treated with or without gemcitabine. Graphs depict results from three independent experiments. Error bars represent S.E. * denotes p

    Journal: The Journal of Biological Chemistry

    Article Title: ST6Gal-I sialyltransferase promotes chemoresistance in pancreatic ductal adenocarcinoma by abrogating gemcitabine-mediated DNA damage

    doi: 10.1074/jbc.M117.808584

    Figure Lengend Snippet: S2-013 KD cells exhibit enhanced gemcitabine-induced DNA damage. A , representative images of gemcitabine ( Gem )-treated S2-013 cells evaluated by comet assay. B , gemcitabine-treated S2-013 KD cells depict significantly increased tail moment compared with gemcitabine-treated EV cells. C , representative images of S2-013 cells stained for γH2AX foci. D , quantification of γH2AX foci in Suit2-013 EV and KD cells treated with or without gemcitabine. Graphs depict results from three independent experiments. Error bars represent S.E. * denotes p

    Article Snippet: For acute gemcitabine treatments (24–72 h), cells were serum-starved for 4 h prior to treatment with 200 n m gemcitabine (Selleck Chemicals, catalog number S1149) for MiaPaCa-2 and Suit2-013 cells, whereas 400 n m gemcitabine was used for BxPC-3 cells (as they appear to be more inherently resistant).

    Techniques: Single Cell Gel Electrophoresis, Staining

    Gemcitabine depletion of IMC population prevents boney union in segmental defect A) Gemcitabine treatment results in significant depletion of Gr-1+CD11b+ IMC. B) H E staining and radiography of unhealed area in femoral segmental defect in wild-type mice (top) and gemcitabine treated mice (bottom) at 21 days post fracture. Relative quantitation of unhealed area following gemcitabine treatment, as compared to control is given on the right. Black arrows indicate fracture site, and failure to heal in gemcitabine-treated mice. (P

    Journal: Bone

    Article Title: Immature myeloid cells are critical for enhancing bone fracture healing through angiogenic cascade

    doi: 10.1016/j.bone.2016.09.018

    Figure Lengend Snippet: Gemcitabine depletion of IMC population prevents boney union in segmental defect A) Gemcitabine treatment results in significant depletion of Gr-1+CD11b+ IMC. B) H E staining and radiography of unhealed area in femoral segmental defect in wild-type mice (top) and gemcitabine treated mice (bottom) at 21 days post fracture. Relative quantitation of unhealed area following gemcitabine treatment, as compared to control is given on the right. Black arrows indicate fracture site, and failure to heal in gemcitabine-treated mice. (P

    Article Snippet: To specifically deplete the IMC population, mice were injected intraperitoneally (IP) with gemcitabine (LKT Laboratories) at a dosing of 60 mg/kg in 100 μl.

    Techniques: Staining, Mouse Assay, Quantitation Assay

    NL induces higher levels of caspase activity compared to current PDAC therapeutic agents MIA PaCa-2 and BXPC-3 cells were treated with 5 µM NL, 5 µM Sorafenib (SRF), 5 µM Gemcitabine (GMC), or 5 µM Curcumin (CUR). (A–C) Caspase-3, -8 and -9 activities in MIA PaCa-2 cells after 24 h of NL, SRF, and GMC treatment. (D) Caspase-3 activity in BXPC-3 cells after 24 h of NL, SRF, and GMC treatment. (E) Caspase-3 activity in MIA PaCa-2 cells after 24 h of NL and CUR treatment. (F) Images of RWPE-1, MIA PaCa-2, and BXPC-3 cells treated with NL for 24 h and 48 h. Data are mean ± SD, n = 3 and presented as fold-change compared to respective controls. Statistical significance was determined by a t-test: *p

    Journal: Cancer letters

    Article Title: Nimbolide reduces CD44 positive cell population and induces mitochondrial apoptosis in pancreatic cancer cells

    doi: 10.1016/j.canlet.2017.10.029

    Figure Lengend Snippet: NL induces higher levels of caspase activity compared to current PDAC therapeutic agents MIA PaCa-2 and BXPC-3 cells were treated with 5 µM NL, 5 µM Sorafenib (SRF), 5 µM Gemcitabine (GMC), or 5 µM Curcumin (CUR). (A–C) Caspase-3, -8 and -9 activities in MIA PaCa-2 cells after 24 h of NL, SRF, and GMC treatment. (D) Caspase-3 activity in BXPC-3 cells after 24 h of NL, SRF, and GMC treatment. (E) Caspase-3 activity in MIA PaCa-2 cells after 24 h of NL and CUR treatment. (F) Images of RWPE-1, MIA PaCa-2, and BXPC-3 cells treated with NL for 24 h and 48 h. Data are mean ± SD, n = 3 and presented as fold-change compared to respective controls. Statistical significance was determined by a t-test: *p

    Article Snippet: Gemcitabine was purchased from Enzo Life Sciences (Farmingdale, NY, USA).

    Techniques: Activity Assay

    Drug sensitivity test in BAP1 knockdown GBC cell line. Cell viability of BAP1 knocked-down GBC cell line G-415 under the agents of gemcitabine (GEM), cisplatin (CDDP), fluorouracil (5-FU), sodium valproate, 5-azacytidine, and bortezomib was measured by MTS assay. No change in sensitivity was observed in GEM, CDDP, 5-FU, sodium valproate or 5-azacytidine. Bortezomib showed a significant decrease in sensitivity in the siRNA1 and siRNA2 group compared to the control.

    Journal: PLoS ONE

    Article Title: Loss of BAP1 expression is associated with genetic mutation and can predict outcomes in gallbladder cancer

    doi: 10.1371/journal.pone.0206643

    Figure Lengend Snippet: Drug sensitivity test in BAP1 knockdown GBC cell line. Cell viability of BAP1 knocked-down GBC cell line G-415 under the agents of gemcitabine (GEM), cisplatin (CDDP), fluorouracil (5-FU), sodium valproate, 5-azacytidine, and bortezomib was measured by MTS assay. No change in sensitivity was observed in GEM, CDDP, 5-FU, sodium valproate or 5-azacytidine. Bortezomib showed a significant decrease in sensitivity in the siRNA1 and siRNA2 group compared to the control.

    Article Snippet: For drug sensitivity, BAP1 knocked-down cells were incubated on 96-well plates for 3 days after administration of the drugs, gemcitabine (GEM; Wako, Osaka, Japan), fluorouracil (5-FU; Wako), cisplatin (CDDP; Wako), sodium valproate (Wako), 5-azacytidine (Wako), and bortezomib (Wako).

    Techniques: MTS Assay

    Body weight change of animals treated with TH-302 (T) in combination with gemcitabine (G) and nab-paclitaxel (nP) in tumor-bearing immunocomprised mice and immunocompetent mice. T was given at 50 mg/kg, ip, G was given at 60 mg/kg ip and nP was given at 30 mg/kg, iv; all drugs were dosed at a Q3Dx5 regimen. ( A - D ), in Hs766t, MIA PaCa-2, PANC-1 and BxPC-3 tumor-bearing nu/nu mice, respectively, n = 10 per group; ( E ), in CD-1 female mice, n = 6 per group; and ( F ), in CD-1 male mice, n = 10 per group. Data represent Mean ± SEM. Arrow, dosing time.

    Journal: Cancer Biology & Therapy

    Article Title: Efficacy and safety of the hypoxia-activated prodrug TH-302 in combination with gemcitabine and nab-paclitaxel in human tumor xenograft models of pancreatic cancer

    doi: 10.1080/15384047.2014.1003005

    Figure Lengend Snippet: Body weight change of animals treated with TH-302 (T) in combination with gemcitabine (G) and nab-paclitaxel (nP) in tumor-bearing immunocomprised mice and immunocompetent mice. T was given at 50 mg/kg, ip, G was given at 60 mg/kg ip and nP was given at 30 mg/kg, iv; all drugs were dosed at a Q3Dx5 regimen. ( A - D ), in Hs766t, MIA PaCa-2, PANC-1 and BxPC-3 tumor-bearing nu/nu mice, respectively, n = 10 per group; ( E ), in CD-1 female mice, n = 6 per group; and ( F ), in CD-1 male mice, n = 10 per group. Data represent Mean ± SEM. Arrow, dosing time.

    Article Snippet: Gemcitabine for Injection (38 mg/ml) (Hospira) and nab-paclitaxel (Abraxane®) for Injectable Suspension (Celgene) were purchased.

    Techniques: Mouse Assay

    Effect of TH-302 (T) in combination with gemcitabine (G) and nab-paclitaxel (nP) on mechanical hyperalgesia, analyzed by von Frey Assay. T was given at 50 mg/kg, ip, G was given at 60 mg/kg ip and nP was given at 30 mg/kg, iv; all drugs were dosed at a Q3Dx5 regimen. Data represent Mean ± SEM of 10 male CD-1 mice each group. Arrow, dosing time.

    Journal: Cancer Biology & Therapy

    Article Title: Efficacy and safety of the hypoxia-activated prodrug TH-302 in combination with gemcitabine and nab-paclitaxel in human tumor xenograft models of pancreatic cancer

    doi: 10.1080/15384047.2014.1003005

    Figure Lengend Snippet: Effect of TH-302 (T) in combination with gemcitabine (G) and nab-paclitaxel (nP) on mechanical hyperalgesia, analyzed by von Frey Assay. T was given at 50 mg/kg, ip, G was given at 60 mg/kg ip and nP was given at 30 mg/kg, iv; all drugs were dosed at a Q3Dx5 regimen. Data represent Mean ± SEM of 10 male CD-1 mice each group. Arrow, dosing time.

    Article Snippet: Gemcitabine for Injection (38 mg/ml) (Hospira) and nab-paclitaxel (Abraxane®) for Injectable Suspension (Celgene) were purchased.

    Techniques: Mouse Assay

    Antitumor efficacy of TH-302 (T) in combination with gemcitabine (G) and nab-paclitaxel (nP) in 4 PDAC xenograft models: Hs766t ( A and B ), MIA PaCa-2 ( C and D ), PANC-1 ( E and F ) and BxPC-3 ( G and H ), n = 10 for each group. T was given at 50 mg/kg, ip, G was given at 60 mg/kg ip and nP was given at 30 mg/kg, iv; all drugs were dosed at a Q3Dx5 regimen. A , C , E , and G , tumor growth was monitored and quantified twice a week. Data represent Mean ± SEM. B , D , F and H , Kaplan-Meier analysis plot using tumor size of 1000 mm 3 as end-point. V, vehicle; Arrow, dosing time.

    Journal: Cancer Biology & Therapy

    Article Title: Efficacy and safety of the hypoxia-activated prodrug TH-302 in combination with gemcitabine and nab-paclitaxel in human tumor xenograft models of pancreatic cancer

    doi: 10.1080/15384047.2014.1003005

    Figure Lengend Snippet: Antitumor efficacy of TH-302 (T) in combination with gemcitabine (G) and nab-paclitaxel (nP) in 4 PDAC xenograft models: Hs766t ( A and B ), MIA PaCa-2 ( C and D ), PANC-1 ( E and F ) and BxPC-3 ( G and H ), n = 10 for each group. T was given at 50 mg/kg, ip, G was given at 60 mg/kg ip and nP was given at 30 mg/kg, iv; all drugs were dosed at a Q3Dx5 regimen. A , C , E , and G , tumor growth was monitored and quantified twice a week. Data represent Mean ± SEM. B , D , F and H , Kaplan-Meier analysis plot using tumor size of 1000 mm 3 as end-point. V, vehicle; Arrow, dosing time.

    Article Snippet: Gemcitabine for Injection (38 mg/ml) (Hospira) and nab-paclitaxel (Abraxane®) for Injectable Suspension (Celgene) were purchased.

    Techniques:

    Effect of TH-302 (T) in combination with gemcitabine (G) and nab-paclitaxel (nP) on tumor cells. PANC-1 tumor bearing animals received T, 50 mg/kg, ip; G, 60 mg/kg ip; and nP 30 mg/kg, iv, at a Q3Dx5 regimen. Tumors were collected 24 hrs after the last treatment. ( A ), representative images of Masson's Trichrome histology staining, TUNEL staining, Caspase-3, γH2AX, and Ki67 immunostaining in vehicle (V), T alone, G + nP doublet and G + nP + T triplet groups. Morphometric analysis of ( B ), necrotic fraction in the whole tumor by Masson's Trichrome; ( C ), number of TUNEL-positive apoptotic cells; ( D ), percentage of Caspase-3 positive apoptotic cells; ( E ), number of γH2AX positive DNA damage cells; and ( F ) number of Ki67 positive proliferative cells. *, P

    Journal: Cancer Biology & Therapy

    Article Title: Efficacy and safety of the hypoxia-activated prodrug TH-302 in combination with gemcitabine and nab-paclitaxel in human tumor xenograft models of pancreatic cancer

    doi: 10.1080/15384047.2014.1003005

    Figure Lengend Snippet: Effect of TH-302 (T) in combination with gemcitabine (G) and nab-paclitaxel (nP) on tumor cells. PANC-1 tumor bearing animals received T, 50 mg/kg, ip; G, 60 mg/kg ip; and nP 30 mg/kg, iv, at a Q3Dx5 regimen. Tumors were collected 24 hrs after the last treatment. ( A ), representative images of Masson's Trichrome histology staining, TUNEL staining, Caspase-3, γH2AX, and Ki67 immunostaining in vehicle (V), T alone, G + nP doublet and G + nP + T triplet groups. Morphometric analysis of ( B ), necrotic fraction in the whole tumor by Masson's Trichrome; ( C ), number of TUNEL-positive apoptotic cells; ( D ), percentage of Caspase-3 positive apoptotic cells; ( E ), number of γH2AX positive DNA damage cells; and ( F ) number of Ki67 positive proliferative cells. *, P

    Article Snippet: Gemcitabine for Injection (38 mg/ml) (Hospira) and nab-paclitaxel (Abraxane®) for Injectable Suspension (Celgene) were purchased.

    Techniques: Staining, TUNEL Assay, Immunostaining

    ( See previous page ). Effect of TH-302 (T) in combination with gemcitabine (G) and nab-paclitaxel (nP) on tumor microenvironment. PANC-1 tumor bearing animals received T, 50 mg/kg, ip; G, 60 mg/kg ip; and nP 30 mg/kg, iv, at a Q3Dx5 regimen. Tumors were collected 24 hrs after the last treatment. ( A ), representative images of Picrosirius red histology staining, α-smooth muscle actin (α-SMA) and pimonidazole immunostaining in vehicle (V), T alone, G + nP doublet and G + nP + T triplet groups. Morphometric analysis of ( B ) percentage of extracellular collagen by Picrosirius red staining; ( C ) percentage of α-SMA positivity inside the tumor; and ( D ) hypoxic fraction in the whole tumor by pimonidazole immunostaining. *, p

    Journal: Cancer Biology & Therapy

    Article Title: Efficacy and safety of the hypoxia-activated prodrug TH-302 in combination with gemcitabine and nab-paclitaxel in human tumor xenograft models of pancreatic cancer

    doi: 10.1080/15384047.2014.1003005

    Figure Lengend Snippet: ( See previous page ). Effect of TH-302 (T) in combination with gemcitabine (G) and nab-paclitaxel (nP) on tumor microenvironment. PANC-1 tumor bearing animals received T, 50 mg/kg, ip; G, 60 mg/kg ip; and nP 30 mg/kg, iv, at a Q3Dx5 regimen. Tumors were collected 24 hrs after the last treatment. ( A ), representative images of Picrosirius red histology staining, α-smooth muscle actin (α-SMA) and pimonidazole immunostaining in vehicle (V), T alone, G + nP doublet and G + nP + T triplet groups. Morphometric analysis of ( B ) percentage of extracellular collagen by Picrosirius red staining; ( C ) percentage of α-SMA positivity inside the tumor; and ( D ) hypoxic fraction in the whole tumor by pimonidazole immunostaining. *, p

    Article Snippet: Gemcitabine for Injection (38 mg/ml) (Hospira) and nab-paclitaxel (Abraxane®) for Injectable Suspension (Celgene) were purchased.

    Techniques: Polyacrylamide Gel Electrophoresis, Staining, Immunostaining

    Effect of TH-302 (T) in combination with gemcitabine (G) and nab-paclitaxel (nP) on hematologic change and blood chemistry changes PANC-1 tumor bearing nude mice and CD1 mice. The means and standard errors from the 6 mice per group are presented. ( A ) blood samples were collected 24 hrs after the last treatment from non-tumor bearing CD-1 mice. ( B ) blood samples were collected 24 hrs after the last treatment from PANC-1 bearing nude mice. C, blood samples were collected 30 days after the last treatment from non-tumor bearing CD-1 mice. ( A-C ), y axis label is cell number (x10 3 /μl). ( D ), plasma samples were collected 24 hrs after the last treatment from non-tumor bearing CD-1 mice. T was given at 50 mg/kg, ip, G was given at 60 mg/kg ip and nP was given at 30 mg/kg, iv; all drugs were dosed at a Q3Dx5 regimen. *, P

    Journal: Cancer Biology & Therapy

    Article Title: Efficacy and safety of the hypoxia-activated prodrug TH-302 in combination with gemcitabine and nab-paclitaxel in human tumor xenograft models of pancreatic cancer

    doi: 10.1080/15384047.2014.1003005

    Figure Lengend Snippet: Effect of TH-302 (T) in combination with gemcitabine (G) and nab-paclitaxel (nP) on hematologic change and blood chemistry changes PANC-1 tumor bearing nude mice and CD1 mice. The means and standard errors from the 6 mice per group are presented. ( A ) blood samples were collected 24 hrs after the last treatment from non-tumor bearing CD-1 mice. ( B ) blood samples were collected 24 hrs after the last treatment from PANC-1 bearing nude mice. C, blood samples were collected 30 days after the last treatment from non-tumor bearing CD-1 mice. ( A-C ), y axis label is cell number (x10 3 /μl). ( D ), plasma samples were collected 24 hrs after the last treatment from non-tumor bearing CD-1 mice. T was given at 50 mg/kg, ip, G was given at 60 mg/kg ip and nP was given at 30 mg/kg, iv; all drugs were dosed at a Q3Dx5 regimen. *, P

    Article Snippet: Gemcitabine for Injection (38 mg/ml) (Hospira) and nab-paclitaxel (Abraxane®) for Injectable Suspension (Celgene) were purchased.

    Techniques: Mouse Assay

    SLC7A11-AS1 Scavenges ROS to Promote Cancer Stemness (A–C) Effects of SLC7A11-AS1 knockdown on expressions of Oct4 and Nanog were determined by qRT-PCR (A and B) and western blot (C) in gemcitabine-resistant PDAC cells (n = 3). (D) Expressions of Oct4 and Nanog in tumor tissues (as described in Figure 1 G) were determined by western blot (D). (E) Oncosphere-formation assay in SLC7A11-AS1 -knockdown and control gemcitabine-resistant PDAC cells. Original magnification ×10. (F) qRT-PCR analysis of SLC7A11-AS1 expression in spheroids and paired attached PDAC cells (n = 3). (G) Flow cytometry analysis of ROS using probe DCFH-DA (upper) and western blot analysis of Oct4 and Nanog (bottom) in SLC7A11-AS1 -knockdown and control PANC-1 cells treated with or without NAC (10 mM) for 48 h (n = 3). *p

    Journal: Molecular Therapy. Nucleic Acids

    Article Title: lncRNA SLC7A11-AS1 Promotes Chemoresistance by Blocking SCFβ-TRCP-Mediated Degradation of NRF2 in Pancreatic Cancer

    doi: 10.1016/j.omtn.2019.11.035

    Figure Lengend Snippet: SLC7A11-AS1 Scavenges ROS to Promote Cancer Stemness (A–C) Effects of SLC7A11-AS1 knockdown on expressions of Oct4 and Nanog were determined by qRT-PCR (A and B) and western blot (C) in gemcitabine-resistant PDAC cells (n = 3). (D) Expressions of Oct4 and Nanog in tumor tissues (as described in Figure 1 G) were determined by western blot (D). (E) Oncosphere-formation assay in SLC7A11-AS1 -knockdown and control gemcitabine-resistant PDAC cells. Original magnification ×10. (F) qRT-PCR analysis of SLC7A11-AS1 expression in spheroids and paired attached PDAC cells (n = 3). (G) Flow cytometry analysis of ROS using probe DCFH-DA (upper) and western blot analysis of Oct4 and Nanog (bottom) in SLC7A11-AS1 -knockdown and control PANC-1 cells treated with or without NAC (10 mM) for 48 h (n = 3). *p

    Article Snippet: The gemcitabine-resistant subline BxPC-3-Gem was maintained in medium containing 50 nM gemcitabine (LC Laboratories, Woburn, MA, USA).

    Techniques: Quantitative RT-PCR, Western Blot, Tube Formation Assay, Expressing, Flow Cytometry

    SLC7A11-AS1 Knockdown Potentiates Resistant PDAC Cell Response to Gemcitabine (A–C) SLC7A11-AS1 -knockdown and control (A) BxPC-3-Gem, (B) PANC-1, and (C) AsPC-1 cells were treated with gemcitabine (1 μM) for indicated times, and cell viability was analyzed by MTT assay (n = 3). (D and E) Colony formation assays of SLC7A11-AS1 -knockdown and control cells with gemcitabine treatment (1 μM) for 2 weeks (n = 3). Representative images (D) and average number of colonies (E) were shown. (F and G) Subcutaneous xenograft analysis of SLC7A11-AS1 -knockdown and control PANC-1 cells (1.5 × 10 6 ) in nude mice treated with gemcitabine (50 mg/kg body weight) or PBS by intraperitoneal (i.p.) injection every 4 days (n = 4). Tumor volume (F) and weight (G) were shown. *p

    Journal: Molecular Therapy. Nucleic Acids

    Article Title: lncRNA SLC7A11-AS1 Promotes Chemoresistance by Blocking SCFβ-TRCP-Mediated Degradation of NRF2 in Pancreatic Cancer

    doi: 10.1016/j.omtn.2019.11.035

    Figure Lengend Snippet: SLC7A11-AS1 Knockdown Potentiates Resistant PDAC Cell Response to Gemcitabine (A–C) SLC7A11-AS1 -knockdown and control (A) BxPC-3-Gem, (B) PANC-1, and (C) AsPC-1 cells were treated with gemcitabine (1 μM) for indicated times, and cell viability was analyzed by MTT assay (n = 3). (D and E) Colony formation assays of SLC7A11-AS1 -knockdown and control cells with gemcitabine treatment (1 μM) for 2 weeks (n = 3). Representative images (D) and average number of colonies (E) were shown. (F and G) Subcutaneous xenograft analysis of SLC7A11-AS1 -knockdown and control PANC-1 cells (1.5 × 10 6 ) in nude mice treated with gemcitabine (50 mg/kg body weight) or PBS by intraperitoneal (i.p.) injection every 4 days (n = 4). Tumor volume (F) and weight (G) were shown. *p

    Article Snippet: The gemcitabine-resistant subline BxPC-3-Gem was maintained in medium containing 50 nM gemcitabine (LC Laboratories, Woburn, MA, USA).

    Techniques: MTT Assay, Mouse Assay, Injection

    Overexpression of SLC7A11-AS1 in Gemcitabine-Resistant PDAC Cells Reduces Intracellular ROS Level (A and B) PDAC cells with acquired (A, BxPC-3-Gem vs BxPC-3) or innate (B, PANC-1 and AsPC-1 vs CFPAC-1) gemcitabine resistance were incubated with probe DCFH-DA (10 μM) for 30 min. ROS levels were detected by flow cytometry. (C) The log2 fold changes of lncRNAs and their nearby coding genes that are associated with ROS regulation were presented by heatmap. (D and E) Expression of SLC7A11-AS1 in PDAC cell lines with aquired (D) or innate drug resistance (E) was detected by qRT-PCR and normalized to GAPDH (n = 3). (F) ROS levels were determined in gemcitabine-resistant PDAC cells with SLC7A11-AS1 knockdown or control as described in (A) and (B). (G and H) SLC7A11-AS1 -knockdown and control PANC-1 cells (1.5 × 10 6 ) were inoculated in BALB/c nude mice (n = 5). Slides from tumor tissues were incubated with DHE for in situ detection of ROS. (G and H) Fluorescence was detected by fluorescent microscope (G) and quantified by using ImageJ (H) (n = 3). *p

    Journal: Molecular Therapy. Nucleic Acids

    Article Title: lncRNA SLC7A11-AS1 Promotes Chemoresistance by Blocking SCFβ-TRCP-Mediated Degradation of NRF2 in Pancreatic Cancer

    doi: 10.1016/j.omtn.2019.11.035

    Figure Lengend Snippet: Overexpression of SLC7A11-AS1 in Gemcitabine-Resistant PDAC Cells Reduces Intracellular ROS Level (A and B) PDAC cells with acquired (A, BxPC-3-Gem vs BxPC-3) or innate (B, PANC-1 and AsPC-1 vs CFPAC-1) gemcitabine resistance were incubated with probe DCFH-DA (10 μM) for 30 min. ROS levels were detected by flow cytometry. (C) The log2 fold changes of lncRNAs and their nearby coding genes that are associated with ROS regulation were presented by heatmap. (D and E) Expression of SLC7A11-AS1 in PDAC cell lines with aquired (D) or innate drug resistance (E) was detected by qRT-PCR and normalized to GAPDH (n = 3). (F) ROS levels were determined in gemcitabine-resistant PDAC cells with SLC7A11-AS1 knockdown or control as described in (A) and (B). (G and H) SLC7A11-AS1 -knockdown and control PANC-1 cells (1.5 × 10 6 ) were inoculated in BALB/c nude mice (n = 5). Slides from tumor tissues were incubated with DHE for in situ detection of ROS. (G and H) Fluorescence was detected by fluorescent microscope (G) and quantified by using ImageJ (H) (n = 3). *p

    Article Snippet: The gemcitabine-resistant subline BxPC-3-Gem was maintained in medium containing 50 nM gemcitabine (LC Laboratories, Woburn, MA, USA).

    Techniques: Over Expression, Incubation, Flow Cytometry, Expressing, Quantitative RT-PCR, Mouse Assay, In Situ, Fluorescence, Microscopy

    Therapeutic efficacy of Gemcitabine combined with iRGD for human NSCLC xenografts. (A) The tumor volume curve during treatment. Arrows indicate the time of injection. The day when treatment started was recorded as day 0. Tumor volume was measured once every three days until day 30. (B) Average tumor weight of each group at the end of treatment. (C) The body weight shift curve of the mice during the experiment. n = 6. Error bars, mean ± SD; ns, not significant; *** p

    Journal: PLoS ONE

    Article Title: A Novel Strategy to Improve the Therapeutic Efficacy of Gemcitabine for Non-Small Cell Lung Cancer by the Tumor-Penetrating Peptide iRGD

    doi: 10.1371/journal.pone.0129865

    Figure Lengend Snippet: Therapeutic efficacy of Gemcitabine combined with iRGD for human NSCLC xenografts. (A) The tumor volume curve during treatment. Arrows indicate the time of injection. The day when treatment started was recorded as day 0. Tumor volume was measured once every three days until day 30. (B) Average tumor weight of each group at the end of treatment. (C) The body weight shift curve of the mice during the experiment. n = 6. Error bars, mean ± SD; ns, not significant; *** p

    Article Snippet: In all, 100 mg/kg Gemcitabine (Merck, Darmstadt, Germany), 4 mg/kg iRGD, 100 mg/kg Gemcitabine + 4 mg/kg iRGD in 200 μl of PBS as vehicle, or 200 μl PBS alone were injected into the mice of the four groups via the tail vein.

    Techniques: Injection, Mouse Assay

    Induction of apoptosis by Gemcitabine combined with iRGD. (A) Apoptotic cells in the tumor tissues were detected by a TUNEL assay. TUNEL-positive nuclei are stained brown, and TUNEL-negative nuclei are stained blue. The figures shown here are representative of the six tumors in each group. Arrows indicate the apoptotic bodies. Magnification, × 400; Scale bars = 50 μm. (B) Quantitative analysis of the apoptosis index in each group. The percentage of TUNEL-positive cells was counted from 100 randomly selected tumor cells per section. Five sections were counted per tumor. n = 6; Error bars, mean ± SD; *** p

    Journal: PLoS ONE

    Article Title: A Novel Strategy to Improve the Therapeutic Efficacy of Gemcitabine for Non-Small Cell Lung Cancer by the Tumor-Penetrating Peptide iRGD

    doi: 10.1371/journal.pone.0129865

    Figure Lengend Snippet: Induction of apoptosis by Gemcitabine combined with iRGD. (A) Apoptotic cells in the tumor tissues were detected by a TUNEL assay. TUNEL-positive nuclei are stained brown, and TUNEL-negative nuclei are stained blue. The figures shown here are representative of the six tumors in each group. Arrows indicate the apoptotic bodies. Magnification, × 400; Scale bars = 50 μm. (B) Quantitative analysis of the apoptosis index in each group. The percentage of TUNEL-positive cells was counted from 100 randomly selected tumor cells per section. Five sections were counted per tumor. n = 6; Error bars, mean ± SD; *** p

    Article Snippet: In all, 100 mg/kg Gemcitabine (Merck, Darmstadt, Germany), 4 mg/kg iRGD, 100 mg/kg Gemcitabine + 4 mg/kg iRGD in 200 μl of PBS as vehicle, or 200 μl PBS alone were injected into the mice of the four groups via the tail vein.

    Techniques: TUNEL Assay, Staining

    Figure 6. Alterations in cell viability using SGI-1776 combination therapy with gemcitabine-based chemotherapy in pancreatic cancer cells. To evaluate the combination of SGI-1776 and gemcitabine on cell viability, PANC-1 ( A ) and MIA PaCa-2 ( B

    Journal: Cancer Biology & Therapy

    Article Title: Inhibition of oncogenic Pim-3 kinase modulates transformed growth and chemosensitizes pancreatic cancer cells to gemcitabine

    doi: 10.4161/cbt.24343

    Figure Lengend Snippet: Figure 6. Alterations in cell viability using SGI-1776 combination therapy with gemcitabine-based chemotherapy in pancreatic cancer cells. To evaluate the combination of SGI-1776 and gemcitabine on cell viability, PANC-1 ( A ) and MIA PaCa-2 ( B

    Article Snippet: Gemcitabine (Santa Cruz Biotechnology) was dissolved in Milli-Q water at a concentration of 20 mM.

    Techniques:

    Figure 4. Inhibition of Pim-3 increases gemcitabine-induced apoptosis in pancreatic cancer cell lines. ( A ) To determine sensitivity to gemcitabine, parental PANC-1 and MIA PaCa-2 cells were treated with various concentrations of gemcitabine in

    Journal: Cancer Biology & Therapy

    Article Title: Inhibition of oncogenic Pim-3 kinase modulates transformed growth and chemosensitizes pancreatic cancer cells to gemcitabine

    doi: 10.4161/cbt.24343

    Figure Lengend Snippet: Figure 4. Inhibition of Pim-3 increases gemcitabine-induced apoptosis in pancreatic cancer cell lines. ( A ) To determine sensitivity to gemcitabine, parental PANC-1 and MIA PaCa-2 cells were treated with various concentrations of gemcitabine in

    Article Snippet: Gemcitabine (Santa Cruz Biotechnology) was dissolved in Milli-Q water at a concentration of 20 mM.

    Techniques: Inhibition

    D5D- KD and DGLA treatment enhanced efficacy of gemcitabine on cell migration and invasion in BxPC-3 cells. A) Transwell migration assay of D5D- KD BxPC-3 cells upon treatment of DGLA (100 µM), gemcitabine (0.1 µM) alone or gemcitabine+DGLA. The D5D- KD cells without fatty acid and drug treatment were used as controls; B) Transwell invasion assay of D5D- KD BxPC-3 cells upon treatment of DGLA (100 µM), gemcitabine (0.1 µM) alone or gemcitabine+DGLA. The D5D- KD cells without fatty acid and drug treatment were used as controls; C) Western blot and protein expression level of acetyl histone H3, MMP-2, MMP-9, E-cadherin, vimentin and snail from D5D- KD BxPC-3 cells treated with vehicle (control), DGLA (100 μM), gemcitabine (0.1 μM) or gemcitabine+DGLA. Protein expression rate was normalized using β-actin as loading control (*: significant difference vs. control with p

    Journal: Redox Biology

    Article Title: Inhibition of cancer migration and invasion by knocking down delta-5-desaturase in COX-2 overexpressed cancer cells

    doi: 10.1016/j.redox.2017.01.016

    Figure Lengend Snippet: D5D- KD and DGLA treatment enhanced efficacy of gemcitabine on cell migration and invasion in BxPC-3 cells. A) Transwell migration assay of D5D- KD BxPC-3 cells upon treatment of DGLA (100 µM), gemcitabine (0.1 µM) alone or gemcitabine+DGLA. The D5D- KD cells without fatty acid and drug treatment were used as controls; B) Transwell invasion assay of D5D- KD BxPC-3 cells upon treatment of DGLA (100 µM), gemcitabine (0.1 µM) alone or gemcitabine+DGLA. The D5D- KD cells without fatty acid and drug treatment were used as controls; C) Western blot and protein expression level of acetyl histone H3, MMP-2, MMP-9, E-cadherin, vimentin and snail from D5D- KD BxPC-3 cells treated with vehicle (control), DGLA (100 μM), gemcitabine (0.1 μM) or gemcitabine+DGLA. Protein expression rate was normalized using β-actin as loading control (*: significant difference vs. control with p

    Article Snippet: Gemcitabine was purchased from Cayman Chemicals (MI, USA).

    Techniques: Migration, Transwell Migration Assay, Transwell Invasion Assay, Western Blot, Expressing