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Berlin Brandenburg

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  • 1
    Language: English
    In: Oncology Reports, January 2005, Vol.13(1), pp.157-160
    Description: Aphidicolin, a tetracyclic diterpene antibiotic produced by Cephalosporium aphidicola, is under investigation as anti-cancer drug. Because of its poor solubility in water, it cannot be administered directly in vivo. Systemic application of aphidicolin glycinate or aphidicolin γ-cyclodextrin complexes resulted in tumour growth inhibition but not in cures. To improve the pharmacokinetics, a liposomal preparation of aphidicolin was developed and tested in neuroblastoma-bearing (UKF-NB-3) mice. The loading capacity of these liposomes was limited. Therefore, 4.5 mg aphidicolin/kg body weight was the maximum aphidicolin dose that could be applied as liposomal preparation in this approach. Comparison of effects on tumour growth exhibited by aphidicolin liposomes (4.5 mg aphidicolin/kg) given for 15 consecutive days to those of γ-cyclodextrin inclusion complexes (15 mg aphidicolin/kg) revealed comparable tumour growth inhibition, although aphidicolin concentrations were approximately 3-fold lower. This shows that liposomal encapsulation is a promising strategy for the improvement of systemic anti-cancer activity of aphidicolin.
    Keywords: Antibiotics, Antineoplastic -- Administration & Dosage ; Aphidicolin -- Administration & Dosage ; Neuroblastoma -- Drug Therapy;
    ISSN: 1021-335X
    E-ISSN: 17912431
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  • 2
    In: Anti-Cancer Drugs, 2001, Vol.12(5), pp.467-473
    Description: Treatment failure in most neuroblastoma (NB) patients is related to primary and/or acquired resistance to conventional chemotherapeutic agents. Aphidicolin (APH), a tetracyclic diterpene, exhibits specific cytotoxic action against NB cells. The purpose of this study was to compare antitumoral efficacy of APH in parental NB cell lines and cell subclones that exhibit drug resistance to vincristine (VCR), doxorubicin (DOX) and cisplatin. Due to poor solubility of APH in water, γ-cyclodextrin (γ-CD) inclusion complexes of APH were used for systemic treatment of xenotransplanted parental and VCR-resistant UKF-NB-3 tumours. APH and its γ-CD inclusion complexes inhibited growth of parental and drug-resistant NB cells at equimolar doses in vitro. Growth of VCR-sensitive and -resistant NB tumors was inhibited at equal doses in a dose-dependent fashion in vivo. These results indicate that the specific cytotoxic activity of APH against NB cells in vitro and in vivo is independent of cellular mechanisms facilitating drug resistance to conventional chemotherapeutic drugs. Hence, taking into account our previous findings that APH acts synergistically with VCR and DOX, APH might be an additive tool for the therapy of NB and is suitable for evaluation in clinical studies of NB treatment protocols.
    Keywords: Aphidicolin -- Therapeutic Use ; Cell Survival -- Drug Effects ; Cyclodextrins -- Pharmacology ; Enzyme Inhibitors -- Therapeutic Use ; Neuroblastoma -- Drug Therapy ; Tumor Cells, Cultured -- Drug Effects;
    ISSN: 0959-4973
    E-ISSN: 14735741
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  • 3
    Language: English
    In: Cell Biology International, April 1994, Vol.18(4), pp.271-278
    Description: The effects of aphidicolin, a specific inhibitor of DNA polymerase alpha, on cell growth, DNA synthesis and myogenic differentiation in the human alveolar rhabdomyosarcoma cell line KFR were studied. The treatment with aphidicolin at 5 x 10(-6) M concentration, which completely inhibited DNA synthesis and cell growth, induced morphological differentiation of small mononuclear cells to elongated, multinucleated (myotube-like) structures. The morphological differentiation was accompanied by the expression of skeletal muscle myosin; about 30% myosin-positive cells were observed after 14 days of treatment, compared to 2.3% in untreated cultures. The results showed that aphidicolin induces differentiation of human rhabdomyosarcoma cells and that multinucleated myotube-like elements may develop simply by cell fusion without cell division and DNA synthesis.
    Keywords: Biology
    ISSN: 1065-6995
    E-ISSN: 1095-8355
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  • 4
    Language: English
    In: Cancer Letters, 1992, Vol.67(2), pp.199-206
    Description: Aphidicolin is a tetracyclic diterpene antibiotic which is known to inhibit the growth of eucaryotic cells by reversible binding to DNA polymerase alpha without significant effect on cell viability in most common human cell lines. We observed that aphidicolin at a concentration of 5 x 10(-7) M kills all cells of four human neuroblastoma cell lines. In contrast, viability of normal human embryonal cells and of human continuous cell lines including HeLa, H9, A549 and Caco-2 was influenced only moderately by aphidicolin. In addition, neuroblastoma cells were killed after treatment with 5 x 10(-7) M aphidicolin in cocultures with normal embryonal cells which continued to proliferate after removal of aphidicolin. These results show that aphidicolin provides an agent which selectively kills neuroblastoma cells in vitro.
    Keywords: Aphidicolin ; Neuroblastoma Cells ; Cell Killing ; Medicine
    ISSN: 0304-3835
    E-ISSN: 1872-7980
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  • 5
    In: Anti-Cancer Drugs, 2000, Vol.11(6), pp.479-485
    Description: Disseminated neuroblastoma diseases are still indicated by a poor outcome despite treatment regimens including radiation therapy and high-dose chemotherapy with stem cell rescue. Therefore, new substances and treatment regimens are of interest. Aphidicolin (APH), a tetracyclic diterpene antibiotic produced by Cephalosporium aphidicola, has a specific toxicity for neuroblastoma cells. Furthermore, it was shown to enhance the effects of X-ray radiation and chemotherapy on malignant cells. To find new substances, 20 APH derivatives were tested for their anti-neuroblastoma efficacy in vitro in UKF-NB-2 cells. Five derivatives had antitumoral activity in neuroblastoma cells. A relationship between the structure and the antitumoral efficacy showed that the hydroxyl groups at C-3 and C-18 are essential for the antitumoral effects. Furthermore, antitumoral effects of APH in combination with doxorubicin and vincristine, both part of commonly used treatment regimens for disseminated neuroblastoma diseases, were tested in the neuroblastoma cell line UKF-NB-2. APH was found to act synergistically with vincristine and synergistically to additive with doxorubicin depending on the molecular ratio of the substances in combination. This may offer the chance to use APH and its derivatives as additional tools in the treatment of neuroblastomas.
    Keywords: Antineoplastic Agents -- Pharmacology ; Antineoplastic Agents, Phytogenic -- Pharmacology ; Aphidicolin -- Pharmacology ; Cell Survival -- Drug Effects ; Doxorubicin -- Pharmacology ; Enzyme Inhibitors -- Pharmacology ; Neuroblastoma -- Drug Therapy ; Tumor Cells, Cultured -- Drug Effects ; Vincristine -- Pharmacology;
    ISSN: 0959-4973
    E-ISSN: 14735741
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