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    American Association for the Advancement of Science (AAAS)
    Published 2014
    Staff View
    Publication Date:
    2014-06-21
    Publisher:
    American Association for the Advancement of Science (AAAS)
    Print ISSN:
    0036-8075
    Electronic ISSN:
    1095-9203
    Topics:
    Biology
    Chemistry and Pharmacology
    Computer Science
    Medicine
    Natural Sciences in General
    Physics
    Keywords:
    Africa ; Disease/*genetics ; England ; Genetics, Medical/trends ; Genome-Wide Association Study/*trends ; Genomics/*trends ; Health ; Humans ; National Institutes of Health (U.S.) ; United States
    Published by:
    http://www.aaas.org/

    Latest Papers from Table of Contents or Articles in Press
  2. 2
    Staff View
    ISSN:
    1569-8041
    Keywords:
    mitochondrial toxin ; MKT 077 ; phase I trial
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Abstract Background: MKT 077 is a rhodacyanine dye analogue which preferentially accumulates in tumour cell mitochondria. It is cytotoxic to a range of tumours. In this phase I study, MKT 077 was administered as a five-day infusion once every three weeks. Patients and methods: Ten patients, median age 59 (38–70) years, with advanced solid cancers were treated at three dose levels: 30, 40 and 50 mg/m2/day for a total of 18 cycles.31 Phosphorus magnetic resonance spectroscopy (MRS) was used to evaluate the effect of MKT 077 on skeletal muscle mitochondrial function. Results: The predominant toxicity was recurrent reversible functional renal impairment (grade 2, two patients). One patient with renal cancer attained stable disease and the remainder progressive disease. There were no MRS changes in the first or second treatment cycles but one patient received 11 treatment cycles and developed changes consistent with a mitochondrial myopathy. Mean values for all pharmacokinetic parameters were at sub micromolar levels and did not exceed IC50 values (≥1 µM). Conclusions: Because of the renal toxicity, and animal studies showing MKT 077 causes eventual irreversible renal toxicity, further recruitment was halted. The study shows, however, that it is feasible to target mitochondria with rhodacyanine analogues, if drugs with higher therapeutic indices could be developed.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1023/A:1008336904585

    Articles: DFG German National Licenses