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  • Vogel, Jens-Uwe  (6)
  • Neuroblastoma
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  • 1
    Language: English
    In: International Journal of Cancer, 10 March 2003, Vol.104(1), pp.36-43
    Description: Cytotoxic drug treatment of neuroblastoma often leads to the development of drug resistance and may be associated with increased malignancy. To study the effects of long‐term cytotoxic treatment on malignant properties of tumor cells, we established 2 neuroblastoma cell sublines resistant to vincristine (VCR) and doxorubicin (DOX). Both established cell lines (UKF‐NB‐2VCR and UKF‐NB‐2DOX) were highly resistant to VCR, DOX and vice‐versa but retained their sensitivity to cisplatin. UKF‐NB‐2VCR and UKF‐NB‐2DOX expressed significant amounts of P‐glycoprotein, while parental cells were P‐glycoprotein negative. GD2 expression was upregulated, whereas NCAM expression was decreased in both resistant cells. Spectral karyotype (SKY) analysis revealed complex aberrant karyotypes in all cell lines and additional acquired karyotype changes in both resistant cells. All cell lines harbored high levels of N‐myc amplification. Compared to parental cells, UKF‐NB‐2VCR and UKF‐NB‐2DOX exhibited more than 2‐fold increase in clonal growth , accelerated adhesion and transendothelial penetration and higher tumorigenicity . We conclude that development of drug resistance and acquisition of certain karyotypic alterations is associated with an increase of additional malignant properties that may contribute to the poor prognosis in advanced forms of NB. The 2 novel neuroblastoma cell sublines also provide useful models for the study of drug resistance in aggressive forms of neuroblastoma. © 2002 Wiley‐Liss, Inc.
    Keywords: Neuroblastoma ; Drug Resistance ; Mdr‐1 ; Ncam ; Gd2 ; Karyotype
    ISSN: 0020-7136
    E-ISSN: 1097-0215
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  • 2
    Language: English
    In: International Journal of Oncology, January 2002, Vol.20(1), pp.97-106
    Description: Valproic acid (VPA) has been shown to induce growth-arrest and differentiation of human neuroectodermal tumors similarly to several other fatty acids. In the present study, we show that continuous VPA treatment together with Interferon-α (INF-α) synergistically inhibited cell growth of a well-established model of neuroblastoma (NB) differentiation using the human N-myc amplified cell line BE(2)-C. Suppression of tumor growth was accompanied by morphological features of neuronal differentiation and inhibition of histone deacetylase activity. Furthermore, induction of differentiation was concomitant with altered expression of genes related to malignant phenotype such as down-regulation of N-myc, induction of bcl-2 and neural cell adhesion molecule. Production of inhibitors of angiogenesis like thrombospondin-1 and activin A was up-regulated in differentiated NB cells. Treatment with VPA alone decreased the ability of BE(2)-C cells to adhere to and penetrate human endothelium. All these effects of VPA were significantly enhanced when combined with INF-α which on its own had little or no effect. These results suggest that combination of VPA and INF-α may provide a novel therapeutic strategy for NB due to enhanced inhibition of tumor cell growth, induction of tumor differentiation and suppression of malignant biology by reduced angiogenic and decreased metastatic potentials.
    Keywords: Antineoplastic Agents -- Therapeutic Use ; Brain Neoplasms -- Drug Therapy ; Cell Differentiation -- Drug Effects ; Enzyme Inhibitors -- Therapeutic Use ; Interferon-Alpha -- Therapeutic Use ; Neuroblastoma -- Drug Therapy ; Valproic Acid -- Therapeutic Use;
    ISSN: 1019-6439
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  • 3
    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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  • 4
    Language: English
    In: Biochemical and Biophysical Research Communications, 2005, Vol.326(2), pp.395-401
    Description: In a model of human neuroblastoma (NB) cell lines persistently infected with human cytomegalovirus (HCMV) we previously showed that persistent HCMV infection is associated with an increased malignant phenotype, enhanced drug resistance, and invasive properties. To gain insights into the mechanisms of increased malignancy we analyzed the global changes in cellular gene expression induced by persistent HCMV infection of human neuroblastoma cells by use of high-density oligonucleotide microarrays (HG-U133A, Affymetrix) and RT-PCR. Comparing the gene expression of different NB cell lines with persistently infected cell sub-lines revealed 11 host cell genes regulated in a similar manner throughout all infected samples. Nine of these 11 genes may contribute to the previously observed changes in malignant phenotype of persistently HCMV infected NB cells by influencing invasive growth, apoptosis, angiogenesis, and proliferation. Thus, this work provides the basis for further functional studies.
    Keywords: Neuroblastoma ; Human Cytomegalovirus ; Microarray Analysis ; Oncomodulation ; Biology ; Chemistry ; Anatomy & Physiology
    ISSN: 0006-291X
    E-ISSN: 1090-2104
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  • 5
    Language: English
    In: Cell Communication & Adhesion, 01 January 2002, Vol.9(3), pp.131-147
    Description: The precise function of cell adhesion molecules in the hematogenous phase of neuroblastoma metastasis is poorly understood. The aim of this study was to investigate whether neural cell adhesion molecule (NCAM) modulates neuroblastoma cell (NB) adhesion and transendothelial penetration in a...
    Keywords: Ncam ; Neuroblastoma ; Adhesion ; Biology
    ISSN: 1541-9061
    E-ISSN: 1543-5180
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  • 6
    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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