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  • 1
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Journal of the American Chemical Society 42 (1920), S. 896-904 
    ISSN: 1520-5126
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Journal of the American Chemical Society 55 (1933), S. 4731-4731 
    ISSN: 1520-5126
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 121 (1928), S. 673-674 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] DARWIN'S theory of the origin of species presupposes the occurrence of occasional variants from the parent stock, of which some are preserved and fostered by natural selection. The cause of this natural variation has been sought in various quarters; and indeed it is to be presumed that it is ...
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  • 4
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Genomics 6 (1990), S. 197-203 
    ISSN: 0888-7543
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Developmental Biology 69 (1979), S. 496-505 
    ISSN: 0012-1606
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 235 (1972), S. 32-36 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Molecular hybridization has been used to detect within human tumours RNA sequences that are homologous to the RNA of oncogenic viruses known to cause similar tumours in ...
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  • 7
    ISSN: 1573-0646
    Keywords: vinorelbine ; clonogenic growth ; human tumors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Vinorelbine (5′-nor-anhydrovinblastine) is a semisynthetic vinca alkaloid currently undergoing extensive clinical evaluation. We have studied the antitumor effect of vinorelbine (final concentrations: 8.4–1000.0 ng/ml) against freshly explanted clonogenic cells from 102 human tumors using a capillary soft agar cloning system and have compared the compound's activity with vinblastine, vincristine, vindesine, paclitaxel, docetaxel, and other clinically used anticancer agents. Four specimens were excluded from further analyses (3 bacterial or fungal contamination, 1 benign histology). Fifty-one of the remaining 98 (52%) specimens had adequate colony formation in control capillaries. Vinorelbine showed concentration-dependent antitumor activity against a variety of solid rumors. At clinically relevant concentrations (0.1 × peak plasma concentrations in humans) vinorelbine inhibited 21 of 49 specimens (43%) and was as active as vinblastine, vincristine, vindesine, bleomycin, doxorubicin, 5-fluorouracil, mitomycin-C, cisplatin, methotrexate, and etoposide. However, paclitaxel (71% inhibition, p = 0.006) and docetaxel (78% inhibition, p = 0.002) were significantly more active than vinorelbine. Moreover, vinorelbine showed antitumor activity against several tumor types and in particular against breast cancer but also in non-small cell lung cancer. We conclude that vinorelbine has a wide spectrum of in vitro activity against freshly explanted human tumors and that the clinical activity of this compound against breast cancer and non-small cell lung cancer is reflected in vitro.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Annals of biomedical engineering 28 (2000), S. 916-921 
    ISSN: 1573-9686
    Keywords: Heterogeneity ; Vascular networks ; Mathematical simulations ; Vascular adaptation ; Structural autoregulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract Terminal vascular beds exhibit a high degree of heterogeneity. Pertinent parameters are nonlinearly related, and their distributions are not independent. The classical “typical vessel” approach using averaged values for different vessel classes may not lead to a correct understanding of physiology and pathophysiology of terminal vascular beds. Such problems can be avoided by studying microcirculatory functions at the network level using a combination of experiments and theoretical models. In this approach, distributions and relationships of pertinent parameters are measured in vivo, leading to the development of comprehensive databases. Such databases can be analyzed and complemented by suitable mathematical models, permitting estimation of parameters that are difficult to measure, and critical assessment of quantitative theories and hypotheses for microvascular function. This collaborative process between experimentally and theoretically oriented investigators may be facilitated in the future by the development of web-based repositories of experimental data and theoretical models. © 2000 Biomedical Engineering Society. PAC00: 8719Tt, 8719Uv
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-0646
    Keywords: phase I ; dextran-conjugated doxorubicin ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Coupling of anthracyclines to high-molecular-weight carriers may alter drug disposition and improve antitumor effects. We have performed a clinical phase I trial of doxorubicin coupled to dextran (70000 m.w.). The drug was administered as single dose i.v. every 21–28 days. Thirteen patients have received a total of 24 courses (median 2; range 1–3). At the starting dose of 40 mg/m2 doxorubicin equivalent (DOXeq), WHO grade IV thrombocytopenia was noted in 2/2 patients. WHO grade IV hepatotoxicity and WHO grade III cardiotoxicity were noted in a patient with preexisting heart disease. Five patients were treated with 12.5 mg/m2 DOXeq. Maximal toxicity at this dose level was WHO grade III thrombocytopenia and local phlebitis (WHO grade II) in 1/5 patients, elevation of alkaline phosphatase (WHO grade III) and WHO grade III vomiting in another patient. Subsequently, five patients received 20 mg/m2 DOXeq. Hepatotoxicity was noted in 5/5 patients (1 × WHO grade IV, 1 × WHO grade III). Thrombocytopenia was noted in 3/5 patients (1 × WHO grade IV, 2 × WHO grade III). At 12.5 mg/m2 DOXeq, a patient diagnosed with a malignant fibrous histiocytoma had stable disease for 4 months. Pharmacokinetic analyses of total and free doxorubicin were performed in plasma and urine. The maximum peak plasma concentration (ppc) for total DOX was 12.3 μg/ml at 40 mg/m2 DOXeq. The area under the plasma concentration time curve (AUC) ranged from 28.83–80.21 μg/ml*h with dose-dependent elimination half lives (t1/2α: 0.02–0.87 h;1/2β: 2.69–11.58 h;1/2γ: 41.44–136.58 h). We conclude that the maximal tolerated dose (MTD) of AD-70 using this schedule is 40 mg/m2 DOXeq. The recommended dose for clinical phase II studies is 12.5 mg/m2 DOXeq.
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  • 10
    ISSN: 1573-0646
    Keywords: vinorelbine ; phase I ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have performed a high-dose clinical and pharmacokinetic trial with vinorelbine administered as a bolus injection every 21 days. The aim was to evaluate a schedule with longer treatment intervals than one week and to determine the toxicity pattern of such a schedule. A total of 13 patients (pts) with solid tumors (non-small-cell lung [3 pts], unknown primary [3 pts], mesothelioma [2 pts], colon/rectum, sarcoma, thyroid, head/neck and cervix [1 pt each]) were entered [9 male, 4 female, median age: 56 years (range: 37–69)]. Dose levels were 35, 40 and 45 mg/m2 with a total of 26 cycles administered. At 40 mg/m2, 2/6 pts developed grade 4 granulocytopenia. 1/1 pt at 45 mg/m2 developed a grade 4 leuko- and granulocytopenia. Non-hematological toxicities were mild to moderate. Neurologic toxicity except for constipation was mild. Constipation occurred at 35 mg/m2 in 1/6 pts WHO grade 4, at 40 mg/m2 in 2/6 pts WHO grade 3 and at 45 mg/m2 in 1/1 pt WHO grade 4 and was due to neurotoxicity. No objective antitumor response was observed. Vinorelbine pharmacokinetics were analysed in whole blood and plasma and were similar to previously published studies using ≤30 mg/m2. Our results confirm a high affinity of vinorelbine to corpuscular blood elements. We conclude that the MTD of vinorelbine administered once every 21 days as bolus injection is 40 mg/m2, the dose-limiting toxicities are constipation and granulocytopenia and the recommended dose for subsequent Phase II trials is 35 mg/m2.
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