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Author (up) Allen, S.L.; Lundberg, A.S. file  url
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  Title Amonafide: a potential role in treating acute myeloid leukemia Type Journal Article
  Year 2011 Publication Expert Opinion on Investigational Drugs Abbreviated Journal Expert Opin Investig Drugs  
  Volume 20 Issue 7 Pages 995-1003  
  Keywords Animals; Antineoplastic Agents--pharmacokinetics, therapeutic use; Clinical Trials as Topic--methods; DNA Topoisomerases, Type II--metabolism; Drug Resistance, Neoplasm; Enzyme Inhibitors--pharmacokinetics, therapeutic use; Humans; Leukemia, Myeloid, Acute--drug therapy, enzymology, mortality; Naphthalimides--pharmacokinetics, therapeutic use; Survival Rate--trends; Treatment Outcome  
  Abstract INTRODUCTION: Amonafide is a novel topoisomerase II (Topo II) inhibitor and DNA intercalator that induces apoptotic signaling by blocking the binding of Topo II to DNA. Amonafide retains cytotoxic activity even in the presence of P-glycoprotein (Pgp)-mediated multi-drug resistance (MDR), a major contributor to clinical treatment failure. AREAS COVERED: In vitro, Pgp-mediated transport (efflux) of amonafide from myeloblasts obtained from patients with secondary acute myeloid leukemia (sAML) was significantly less than efflux of daunorubicin. Amonafide has shown efficacy in patients with sAML, as well as in patients with poor prognostic characteristics such as older age and unfavorable cytogenetics, all associated with MDR. Improved antileukemic activity is observed when amonafide is given together with cytarabine, rather than as monotherapy, with a complete remission rate of approximately 40% in a recent Phase II trial in sAML. The efficacy of amonafide was maintained among poor-risk subsets of patients, including older patients and patients who had previous myelodysplastic syndrome or previous leukemogenic therapy. The safety profile was acceptable and manageable. EXPERT OPINION: Amonafide plus cytarabine may have clinical utility in patients with sAML and in other poor-risk subgroups of acute myeloid leukemia (AML). Ongoing trials will help define the role for amonafide in the treatment of poor-risk AML.  
  Call Number Serial 199  
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Author (up) Alonso, A.; Almendral, M.J.; Curto, Y.; Criado, J.J.; Rodriguez, E.; Manzano, J.L. file  url
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  Title Determination of the DNA-binding characteristics of ethidium bromide, proflavine, and cisplatin by flow injection analysis: usefulness in studies on antitumor drugs Type Journal Article
  Year 2006 Publication Analytical Biochemistry Abbreviated Journal Anal Biochem  
  Volume 355 Issue 2 Pages 157-164  
  Keywords Antineoplastic Agents--chemistry, metabolism; Binding Sites; Cisplatin--chemistry, metabolism; DNA--chemistry, metabolism; Ethidium--chemistry, metabolism; Flow Injection Analysis--methods; Fluorescent Dyes; Kinetics; Nucleic Acid Conformation; Proflavine--chemistry, metabolism; Spectrometry, Fluorescence  
  Abstract Flow injection analysis was used to study the reactions occurring between DNA and certain compounds that bind to its double helix, deforming this and even breaking it, such that some of them (e.g., cisplatin) are endowed with antitumoral activity. Use of this technique in the merging zones and stopped-flow modes afforded data on the binding parameters and the kinetic characteristics of the process. The first compound studied was ethidium bromide (EtdBr), used as a fluorescent marker because its fluorescence is enhanced when it binds to DNA. The DNA-EtdBr binding parameters, the apparent intrinsic binding constant (0.31+/-0.02 microM(-1)), and the maximum number of binding sites per nucleotide (0.327+/-0.009) were determined. The modification introduced in these parameters by the presence of proflavine (Prf), a classic competitive inhibitor of the binding of EtdBr to the DNA double helix, was also studied, determining the value of the intrinsic binding constant of Prf (K(Prf) = 0.119+/-9x10(-3) microM(-1)). Finally, we determined the binding parameters between DNA and EtdBr in the presence of the antitumor agent cisplatin, a noncompetitive inhibitor of such binding. This provided information about the binding mechanism as well as the duration and activity of the binding of the compound in its pharmacological use.  
  Call Number Serial 363  
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Author (up) Alvarez, J.; Fadic, R. file  url
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  Title Assembly and disassembly of axonal microtubules of the toad Xenopus laevis under the effect of temperature Type Journal Article
  Year 1992 Publication The Journal of Experimental Zoology Abbreviated Journal J Exp Zool  
  Volume 264 Issue 3 Pages 261-266  
  Keywords Animals; Axons/*physiology; Cytoplasm/metabolism; Kinetics; Microtubules/*physiology; Seasons; *Temperature; Tubulin/metabolism; Xenopus laevis  
  Abstract In toads Xenopus laevis living at 11 degrees (winter), the microtubular density of 4-microns myelinated axons of lumbosacral nerves was assessed with the electron microscope. In controls, the density was 11.2 microtubules/microns2. In nerves incubated at 0 degrees, microtubules decreased following a simple exponential curve with a half time of 4.7 min (k = 0.149 min-1); residual microtubules were 4.5%. After rewarming, the full complement of microtubules reappeared within 60 min. In steady state, the microtubular density exhibited a linear relationship with temperature (range: 0-22 degrees; slope 0.94 microtubules/microns 2 per degree; r, 0.96). After heating the nerve by 11 degrees above the physiological temperature, microtubules increased by 83%, whereby the pool of unpolymerized tubulin was at least 2.7 mg/ml of axoplasm. A seasonal variation of the microtubular density was observed which accorded with the environmental temperature. The macroscopic kinetics of microtubule disassembly in the axoplasm is similar to that reported for purified tubulin but that of assembly is slower. Microtubules of peripheral axons of Xenopus are cold-labile and vary during the annual cycle.  
  Call Number Serial 1174  
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Author (up) Anderson, J.W.; Nicolosi, R.J.; Borzelleca, J.F. file  url
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  Title Glucosamine effects in humans: a review of effects on glucose metabolism, side effects, safety considerations and efficacy Type Journal Article
  Year 2005 Publication Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association Abbreviated Journal Food Chem Toxicol  
  Volume 43 Issue 2 Pages 187-201  
  Keywords Administration, Oral; Animals; Blood Glucose/*drug effects/metabolism; Clinical Trials as Topic; Glucosamine/*adverse effects/pharmacokinetics/therapeutic use; Humans; Infusions, Parenteral; Lethal Dose 50; Metabolic Clearance Rate; Osteoarthritis/*drug therapy; Safety; Toxicity Tests; Treatment Outcome  
  Abstract Glucosamine is widely used to relieve symptoms from osteoarthritis. Its safety and effects on glucose metabolism are critically evaluated in this review. The LD50 of oral glucosamine in animals is approximately 8000 mg/kg with no adverse effects at 2700 mg/kg for 12 months. Because altered glucose metabolism can be associated with parenteral administration of large doses of glucosamine in animals and with high concentrations in in vitro studies, we critically evaluated the clinical importance of these effects. Oral administration of large doses of glucosamine in animals has no documented effects on glucose metabolism. In vitro studies demonstrating effects of glucosamine on glucose metabolism have used concentrations that are 100-200 times higher than tissue levels expected with oral glucosamine administration in humans. We reviewed clinical trial data for 3063 human subjects. Fasting plasma glucose values decreased slightly for subjects after oral glucosamine for approximately 66 weeks. There were no adverse effects of oral glucosamine administration on blood, urine or fecal parameters. Side effects were significantly less common with glucosamine than placebo or non-steroidal anti-inflammatory drugs (NSAID). In contrast to NSAID, no serious or fatal side effects have been reported for glucosamine. Our critical evaluation indicates that glucosamine is safe under current conditions of use and does not affect glucose metabolism.  
  Call Number Serial 1749  
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Author (up) Baselga, J.; Pfister, D.; Cooper, M.R.; Cohen, R.; Burtness, B.; Bos, M.; D'Andrea, G.; Seidman, A.; Norton, L.; Gunnett, K.; Falcey, J.; Anderson, V.; Waksal, H.; Mendelsohn, J. file  url
openurl 
  Title Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin Type Journal Article
  Year 2000 Publication Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology Abbreviated Journal J Clin Oncol  
  Volume 18 Issue 4 Pages 904-914  
  Keywords Adult; Antibodies, Monoclonal/adverse effects/pharmacokinetics/*therapeutic use; Antibodies, Monoclonal, Humanized; Antineoplastic Agents/adverse effects/pharmacokinetics/*therapeutic use; Area Under Curve; Carcinoma, Non-Small-Cell Lung/drug therapy/therapy; Carcinoma, Squamous Cell/drug therapy/therapy; Cetuximab; Cisplatin/*therapeutic use; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms/drug therapy/therapy; Humans; Infusions, Intravenous; Lung Neoplasms/drug therapy/therapy; Male; Neoplasms, Glandular and Epithelial/drug therapy/*therapy; Receptor, Epidermal Growth Factor/*antagonists & inhibitors/genetics; Recombinant Fusion Proteins/adverse effects/pharmacokinetics/*therapeutic use; Remission Induction; Safety  
  Abstract PURPOSE: The epidermal growth factor (EGF) receptor is frequently overexpressed in epithelial tumors. C225 is a human-to-murine chimeric monoclonal antibody that binds to the receptor and inhibits growth of cancer cells expressing the receptor. We evaluated the pharmacokinetics and toxicity of C225 in patients with advanced tumors overexpressing EGF receptors. PATIENTS AND METHODS: We treated 52 patients in three successive phase I clinical trials of C225 as a single dose (n = 13), weekly multiple dose (n = 17), and weekly multiple dose with cisplatin (n = 22). C225 dose levels were 5, 20, 50, and 100 mg/m(2). In the study combining C225 with cisplatin, limited to patients with either head and neck or non-small-cell lung cancer, C225 was further escalated to 200 and 400 mg/m(2). Cisplatin was given at a dose of 60 mg/m(2) once every 4 weeks, and treatment was continued for up to 12 weeks if no disease progression occurred. RESULTS: C225 displayed nonlinear pharmacokinetics, with antibody doses in the range of 200 to 400 mg/m(2) being associated with complete saturation of systemic clearance. C225 clearance did not change with repeated administration or with coadministration of cisplatin. Antibodies against C225 were detected in only one patient, and C225-associated toxicity was minimal. Patients experiencing disease stabilization were seen in all studies. In the study combining C225 and cisplatin, nine (69%) of 13 patients treated with antibody doses >/= 50 mg/m(2) completed 12 weeks of therapy, and two partial responses were observed. CONCLUSION: C225 has dose-dependent pharmacokinetics, and doses that achieve saturation of systemic clearance are well tolerated. C225 given in combination with cisplatin has biologic activity at pharmacologically relevant doses.  
  Call Number Serial 2015  
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