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Berlin Brandenburg

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  • Doerr, H.W.  (30)
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  • 1
    Language: English
    In: Molecular Cancer, 01 September 2009, Vol.8(1), p.80
    Description: Abstract Background Chemoresistance acquisition may influence cancer cell biology. Here, bioinformatics analysis of gene expression data was used to identify chemoresistance-associated changes in neuroblastoma biology. Results Bioinformatics analysis of gene expression data revealed that expression...
    Keywords: Medicine ; Biology
    ISSN: 1476-4598
    E-ISSN: 1476-4598
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  • 2
    In: Scientific Reports, 2015, Vol.5
    Description: Flubendazole was shown to exert anti-leukaemia and anti-myeloma activity through inhibition of microtubule function. Here, flubendazole was tested for its effects on the viability of in total 461 cancer cell lines. Neuroblastoma was identified as highly flubendazole-sensitive cancer entity in a screen of 321 cell lines from 26 cancer entities. Flubendazole also reduced the viability of five primary neuroblastoma samples in nanomolar concentrations thought to be achievable in humans and inhibited vessel formation and neuroblastoma tumour growth in the chick chorioallantoic membrane assay. Resistance acquisition is a major problem in high-risk neuroblastoma. 119 cell lines from a panel of 140 neuroblastoma cell lines with acquired resistance to various anti-cancer drugs were sensitive to flubendazole in nanomolar concentrations. Tubulin-binding agent-resistant cell lines displayed the highest flubendazole IC50 and IC90 values but differences between drug classes did not reach statistical significance. Flubendazole induced p53-mediated apoptosis. The siRNA-mediated depletion of the p53 targets p21, BAX, or PUMA reduced the neuroblastoma cell sensitivity to flubendazole with PUMA depletion resulting in the most pronounced effects. The MDM2 inhibitor and p53 activator nutlin-3 increased flubendazole efficacy while RNAi-mediated p53-depletion reduced its activity. In conclusion, flubendazole represents a potential treatment option for neuroblastoma including therapy-refractory cells.
    Keywords: Biology;
    ISSN: 20452322
    E-ISSN: 20452322
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  • 3
    Language: English
    In: Cancer research, 01 April 2003, Vol.63(7), pp.1508-14
    Description: Replication restricted oncolytic viruses such as multimutated herpes simplex virus type 1 (HSV-1) G207 represent a novel and attractive approach for cancer therapy, including pediatric solid tumors. Rhabdomyosarcoma is the most common soft-tissue sarcoma of childhood and is often diagnosed already as an advanced disseminated disease. Despite aggressive therapeutic approaches, the prognosis for patients with metastatic rhabdomyosarcoma remains grim. Therefore, there is a need for novel effective drugs with superior safety and efficacy profile. In this study, we showed marked in vitro activity of HSV-1 G207 against embryonal and alveolar rhabdomyosarcoma cells. All human embryonal (KF-RMS-1, RD, and CCA) and alveolar RMS (KFR, Rh28, Rh30, and Rh41) cell lines were highly sensitive to cytotoxic and replicative effects of G207 even at a multiplicity of infection of 0.01, except embryonal Rh1 rhabdomyosarcoma cells, which were efficiently killed only upon multiplicity of infection of 1.0. i.v. G207 treatment of xenotransplanted KFR and KF-RMS-1 tumors in mice led to significant tumor growth inhibition of both tumor entities, whereas intraneoplastic G207 treatment additionally resulted in complete tumor disappearance in 25% of animals. No difference has been found between alveolar and embryonal types of rhabdomyosarcoma. Combination treatment of both cell lines with G207 and vincristine led to strongly enhanced in vitro cytotoxicity without affecting infection efficiency and replication of G207 in KFR as well as in KF-RMS-1 cells. In vivo combination treatment using i.v. G207 and vincristine resulted in complete regression of alveolar rhabdomyosarcoma in five of eight animals and significant growth inhibition of embryonal rhabdomyosarcoma. Taking into consideration the proven safety of G207 in humans, we suggest that G207 alone and in combination with vincristine should be additionally evaluated as a potential agent against human rhabdomyosarcoma.
    Keywords: Antineoplastic Agents, Phytogenic -- Pharmacology ; Rhabdomyosarcoma -- Therapy ; Simplexvirus -- Physiology ; Vincristine -- Pharmacology
    ISSN: 0008-5472
    E-ISSN: 15387445
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 4
    Language: English
    In: Biochemical Pharmacology, 15 January 2010, Vol.79(2), pp.130-136
    Description: Artemisinin derivatives are well-tolerated anti-malaria drugs that also exert anti-cancer activity. Here, we investigated artemisinin and its derivatives dihydroartemisinin and artesunate in a panel of chemosensitive and chemoresistant human neuroblastoma cells as well as in primary neuroblastoma cultures. Only dihydroartemisinin and artesunate affected neuroblastoma cell viability with artesunate being more active. Artesunate-induced apoptosis and reactive oxygen species in neuroblastoma cells. Of 16 cell lines and two primary cultures, only UKF-NB-3 CDDP showed low sensitivity to artesunate. Characteristic gene expression signatures based on a previous analysis of artesunate resistance in the NCI60 cell line panel clearly separated UKF-NB-3 CDDP from the other cell lines. -Buthionine-S,R-sulfoximine, an inhibitor of GCL (glutamate–cysteine ligase), resensitised in part UKF-NB-3 CDDP cells to artesunate. This finding together with bioinformatic analysis of expression of genes involved in glutathione metabolism showed that this pathway is involved in artesunate resistance. These data indicate that neuroblastoma represents an artesunate-sensitive cancer entity and that artesunate is also effective in chemoresistant neuroblastoma cells.
    Keywords: Neuroblastoma ; Artesunate ; Artemisinin ; Chemoresistance ; Cancer ; Chemotherapy ; Pharmacy, Therapeutics, & Pharmacology ; Chemistry
    ISSN: 0006-2952
    E-ISSN: 1873-2968
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  • 5
    Language: English
    In: The Journal of Infectious Diseases, 1 September 2000, Vol.182(3), pp.643-651
    Description: In fibroblasts, infection with human cytomegalovirus (HCMV) inhibits expression of the extracellular matrix proteins thrombospondin-1 and -2 (TSP-1 and TSP-2). These effects may depend on expression of HCMV immediate-early (IE) genes, which are activated by cellular transcription factor NF-kB. The influence of HCMV infection on TSP-1 and TSP-2 expression and the ability of different antiviral drugs to prevent these cellular changes in permissive cultures of human retinal glial cells were observed. Ganciclovir inhibited only HCMV late antigen (LA) expression, whereas antisense oligonucleotide ISIS 2922 and peptide SN50, inhibitors of HCMV IE expression and NF-kB activity, respectively, inhibited both IE and LA expression. ISIS 2922 and SN50, but not ganciclovir, prevented down-modulation of TSP1 and TSP-2. The results showed that HCMV-induced down-modulation of TSP-1 and TSP2 in retinal glial cells is prevented by inhibition of HCMV IE expression. These findings may be relevant to pathogenesis and treatment of HCMV retinitis.
    Keywords: Biological sciences -- Biology -- Cytology ; Biological sciences -- Biology -- Microbiology ; Health sciences -- Medical sciences -- Pharmaceutics ; Biological sciences -- Biology -- Microbiology ; Health sciences -- Medical conditions -- Infections ; Biological sciences -- Biochemistry -- Biomolecules ; Physical sciences -- Chemistry -- Chemical compounds ; Biological sciences -- Biology -- Cytology ; Biological sciences -- Biology -- Cytology ; Health sciences -- Medical conditions -- Diseases
    ISSN: 00221899
    E-ISSN: 15376613
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  • 6
    Language: English
    In: International Journal of Cancer, 01/03/1996, Vol.65(1), pp.90-96
    Description: Human neuroblastoma cell line UKF-NB-4 persistently infected with human cytomegalovirus (HCMV) strain AD169 was established to study the effects of long-term HCMV infection on virus production and phenotypic characteristics of tumour cells. The cells designated UKF-NB-4 super(AD169) were subcultured (80 subcultures) over a period of more than 2 years after initiation of infection. UKF-NB-4 super(AD169) cells continued to produce infectious virus in successive passages, with a titre ranging from 9 x 10 super(3) to 1 x 10 super(5) and from 2 x 10 super(1) to 2 x 10 super(2) plaque-forming units per 10 super(6) cells and 1 ml culture medium, respectively; 10-20% of the cells produced HCMV-specific antigens, while 6-13% produced infectious virus progeny. The number of HCMV-specific DNA copies ranged from 9 x 10 super(4) to 9 x 10 super(6) per 10 super(6) cells. Transmission electron microscopy confirmed the productive nature of HCMV infection. UKF-NB-4 super(AD169) cultures proliferated, with population doubling time ranging from 24.5 to 26.6 hr (19.5 to 20.3 hr for UKF-NB-4) and cell viability from 79% to 85% (91-96% for UKF-NB-4). Significantly lower amounts of tyrosine hydroxylase and decreased activity for dopamine- beta -hydroxylase than in uninfected cells were observed in UKF-NB-4 super(AD169) cells. However, the expression of N-myc oncoprotein was significantly increased in persistently infected cultures. Our results show that long-term productive HCMV infection of UKF-NB-4 cell line is associated with the modulation of phenotypic properties, which may be related to the biological behaviour of neuroblastoma cells.
    Keywords: Cytomegalovirus ; Cytomegalovirus ; Neuroblastoma Cells ; Man ; Tumor Cells ; Phenotyping ; Neuroblastoma Cells ; Man ; Tumor Cells ; Phenotyping ; Neurovirology ; Virus Behavior in Cell Culture ; Tyrosine 3-Monooxygenase ; Dopamine Beta -Monooxygenase ; N-Myc Protein ; Tyrosine 3-Monooxygenase ; Dopamine Beta -Monooxygenase ; N-Myc Protein ; N-Myc Protein ; Dopamine Beta -Monooxygenase ; Tyrosine 3-Monooxygenase;
    ISSN: 00207136
    E-ISSN: 10970215
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  • 7
    In: Transplantation, 1996, Vol.62(9), pp.1371-1374
    Description: In this study, we investigated the effects of the intracellular metal chelator desferrioxamine (DFO) and the extracellular metal chelator diethylenetriamine penta-acetic acid (DTPA), which were previously shown to have strong anticytomegalovirus potencies, on their ability to elicit immunomodulatory effects in vitro[fcn,3]. The results showed that nontoxic and in vivo attainable concentrations of both DFO and DTPA inhibited mitogen- and allogen-induced proliferation of peripheral blood lymphocytes. The immunomodulatory effects of DFO/DTPA seem to be due to the impaired expression of interleukin-2 receptor and the reduced secretion of interleukin-2. However, metal chelators were more effective than cyclosporine or tacrolimus (FK506) in our in vitro experiments. Moreover, cytotoxicity mediated by lymphokine-activated killer cells and natural killer cells and the expression of HLA and adhesion molecules on cytokine-stimulated endothelial cells were differentially impaired by DFO/DTPA. These results warrant further study of the immunological effects of metal chelators in vivo.
    Keywords: Immunopharmacology ; Immunoregulation ; Metal Chelators ; Desferrioxamine ; Diethylenetriamine Penta-Acetic Acid ; Desferrioxamine ; Diethylenetriamine Penta-Acetic Acid ; Immunoregulation ; Metal Chelators;
    ISSN: 0041-1337
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  • 8
    Language: English
    In: In Vitro Cellular & Developmental Biology - Animal, 1992, Vol.28(3), pp.147-148
    Keywords: Biological sciences -- Biology -- Cytology ; Biological sciences -- Biology -- Cytology ; Biological sciences -- Biology -- Cytology ; Biological sciences -- Biology -- Cytology ; Applied sciences -- Laboratory techniques -- Culture techniques ; Physical sciences -- Chemistry -- Chemical compounds ; Physical sciences -- Chemistry -- Chemical compounds;
    ISSN: 0883-8364
    E-ISSN: 1543-706X
    E-ISSN: 2327431X
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  • 9
    Language: English
    In: In Vitro Cellular & Developmental Biology, 1990, Vol.26(9), pp.841-842
    Keywords: Biology;
    ISSN: 0883-8364
    E-ISSN: 1475-2689
    E-ISSN: 2327431X
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  • 10
    Language: English
    In: In Vitro Cellular & Developmental Biology, 1 September 1990, Vol.26(9), pp.841-842
    Keywords: Biological sciences -- Biology -- Cytology ; Biological sciences -- Biology -- Cytology ; Biological sciences -- Biology -- Cytology ; Applied sciences -- Laboratory techniques -- Culture techniques ; Biological sciences -- Biology -- Cytology ; Biological sciences -- Biology -- Physiology ; Biological sciences -- Biology -- Cytology ; Business -- Business economics -- Commercial production ; Applied sciences -- Technology -- Storage ; Applied sciences -- Laboratory techniques -- Culture techniques
    ISSN: 08838364
    Source: Archival Journals (JSTOR)
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