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4 protocols using 17 aag

1

Evaluation of Multidrug Resistance Modulators

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Bisantrene, doxorubicin, mitoxantrone, paclitaxel, rhodamine 123, vinblastine and verapamil were purchased from Sigma-Aldrich (St. Louis, MO). BODIPY FL-ethylenediamine (EDA), BODIPY-prazosin, BODIPY-vinblastine, calcein-AM, and tetramethylrhodamine ethyl ester (TMRE) were obtained from Invitrogen/Life Technologies (Carlsbad, CA). Laser dye styryl 751 (LDS 751) was purchased from Santa Cruz Biotechnology (Dallas, TX). Flutax was from Tocris Bioscience (Minneapolis, MN). AT9283, KW2478 and valspodar were from Apex Biotechnology (Houston, TX). YM-155, VX-680, and 17-AAG were purchased from ChemieTek (Indianapolis, IN). Romidepsin was obtained from Selleck Chem (Houston, TX). Elacridar and tariquidar were from MedChemExpress (Monmouth Junction, NJ).
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2

Identifying Anti-Neoplastic Drug Candidates

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A number of anti-neoplastic drugs were tested for their ability to inhibit growth of MM cells: the tyrosine kinase inhibitors (TKI) bosutinib, dasatinib, imatinib, sorafenib, sunitinib, and nilotinib, the ErbB-receptor inhibitors lapatinib, erlotinib, and gefitinib, the Aurora-kinase inhibitor VX-680, the HSP90 inhibitor 17AAG, the PLK-1 inhibitor BI2536, the pan-BCL-2 antagonist obatoclax, and the HDAC-inhibitor vorinostat were purchased from Chemietek (Indianapolis, IN, USA). The PI3 kinase/mTOR inhibitor BEZ235 was obtained from Selleck Chemicals (Houston, TX, USA). Stock solutions of drugs were prepared by dissolving in dimethylsulfoxide, DMSO (Merck, Darmstadt, Germany). RPMI 1640 medium and fetal calf serum (FCS) were purchased from PAA Laboratories (Pasching, Austria), and 3H-thymidine from PerkinElmer (Waltham, MA, USA). FITC-labeled CD34 monoclonal antibody (mAb) 581, PE-labeled CD34 mAb 581, FITC-labeled CD138 mAb MI15, PE-labeled CD138 mAb DL-101, PerCP-labeled CD45 mAb 2D1, APC-labeled CD38 mAb HIT2, PE-labeled and Alexa Fluor® 647-labeled active caspase-3 mAb C92-605 were purchased from BD Biosciences (San Jose, CA, USA). The PerCP-labeled CD20 mAb 2H7 and the APC-labeled CD27 mAb O323 were obtained from Biolegend (San Diego, CA, USA), and an Annexin V/FITC kit from eBioscience (San Diego, CA, USA).
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3

Evaluation of Small Molecule Inhibitors

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17-AAG (tanespimycin), NVP-AUY922, AZD6244, and NVP-BEZ235 were purchased from ChemieTek (Indianapolis, IN) and ES936 and gemcitabine from Tocris Bioscience (Bristol, United Kingdom), and each one of them is dissolved in DMSO or water. Propidium iodide, crystal violet, iodonitrotetrazolium violet, 4-hydroxycoumarin (dicumarol), 2,6-dichlorophenol-indophenol (DCPIP), and oxaliplatin were purchased from Sigma-Aldrich (St Louis, MO).
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4

Small Molecule Screening for Cancer

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Gefitinib, erlotinib, sorafenib, 17-AAG, NVP-BEZ235 and AZD-6244 were obtained from ChemieTek (Indianapolis, IN, USA). Rapamycin, tricostatin (TSA), propidium iodide and 3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) were purchased from Sigma-Aldrich (St. Louis, MO, USA). RNase A was obtained from Serva (Heidelberg, Germany).
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