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Berlin Brandenburg

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  • 1
    Language: English
    In: Neoplasia, December 2010, Vol.12(12), pp.1023,IN10-1030,IN17
    Description: The human immunodeficiency virus (HIV) protease inhibitor saquinavir shows anticancer activity. Although its nitric oxide-modified derivative saquinavir-NO (saq-NO) was less toxic to normal cells, it exerted stronger inhibition of B16 melanoma growth in syngeneic C57BL/6 mice than saquinavir did. Saq-NO has been shown to block proliferation, upregulate p53 expression, and promote differentiation of C6 glioma and B16 cells. The anticancer activity of substances is frequently hampered by cancer cell chemoresistance mechanisms. Therefore, we here investigated the roles of p53 and the ATP-binding cassette (ABC) transporters P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein 1 (BCRP1) in cancer cell sensitivity to saq-NO to get more information about the potential of saq-NO as anticancer drug. Saq-NO exerted anticancer effects in lower concentrations than saquinavir in a panel of human cancer cell lines. Neither p53 mutation or depletion nor expression of P-gp, MRP1, or BCRP1 affected anticancer activity of saq-NO or saquinavir. Moreover, saq-NO sensitized P-gp-, MRP1-, or BCRP1-expressing cancer cells to chemotherapy. Saq-NO induced enhanced sensitization of P-gp- or MRP1-expressing cancer cells to chemotherapy compared with saquinavir, whereas both substances similarly sensitized BCRP1-expressing cells. Washout kinetics and ABC transporter ATPase activities demonstrated that saq-NO is a substrate of P-gp as well as of MRP1. These data support the further investigation of saq-NO as an anticancer drug, especially in multidrug-resistant tumors.
    Keywords: Medicine
    ISSN: 1476-5586
    E-ISSN: 1476-5586
    Source: ScienceDirect Journals (Elsevier)
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  • 2
    In: LaboratoriumsMedizin, 2006, Vol.30(1), pp.23-25
    Description: Bis einschließlich 10. Januar 2006 infizierten sich in Asien rund 150 Menschen mit dem Erreger der Vogelgrippe H5N1. In sechs Ländern (Kambodscha, China, Indonesien, Thailand, Vietnam und Türkei) verstarben an der “Hühnergrippe” rund 80 Patienten. Eine Übertragung von Mensch zu Mensch scheint in Einzelfällen möglich. Eine Pandemie hat der Erreger bisher nicht ausgelöst: Er wurde nicht (effektiv) von Mensch zu Mensch übertragen.
    Description: Aktuell erscheint aber eine Ausweitung der Hühnergrippe auch in Europa denkbar. Meldungen aus Rumänien im Oktober 2005 lassen eine Ausbreitung des H5N1-Erregers bei Wasservögeln vermuten. Jetzt (Stand Januar 2006) wurden auch aus der Türkei mehrere Infektionen des Menschen, davon drei Todesfälle, bekannt.
    Description: Sorge bereitet Experten die Möglichkeit eines genetischen “Reassortment” durch eine gleichzeitige Doppel-Infektion eines Wirtes (Mensch, Schwein) mit humanen und aviären Influenza-A-Viren-Erregern. Der neue Subtyp könnte bei passender Adaption an die menschlichen Zellen zu einer neuen Pandemie führen.
    Keywords: Aviäre Influenza ; Epidemie ; Pandemie ; Avian Flu ; Epidemic ; Pandemic
    ISSN: 0342-3026
    E-ISSN: 0025-8466
    E-ISSN: 14390477
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  • 3
    Language: English
    In: PLoS ONE, 2012, Vol.7(5), p.e36506
    Description: Oncolytic influenza A viruses with deleted NS1 gene (delNS1) replicate selectively in tumour cells with defective interferon response and/or activated Ras/Raf/MEK/ERK signalling pathway. To develop a delNS1 virus with specific immunostimulatory properties, we used an optimised technology to insert the interleukin-15 (IL-15) coding sequence into the viral NS gene segment (delNS1-IL-15). DelNS1 and delNS1-IL-15 exerted similar oncolytic effects. Both viruses replicated and caused caspase-dependent apoptosis in interferon-defective melanoma cells. Virus replication was required for their oncolytic activity. Cisplatin enhanced the oncolytic activity of delNS1 viruses. The cytotoxic drug increased delNS1 replication and delNS1-induced caspase-dependent apoptosis. Interference with MEK/ERK signalling by RNAi-mediated depletion or the MEK inhibitor U0126 did not affect the oncolytic effects of the delNS1 viruses. In oncolysis sensitive melanoma cells, delNS1-IL-15 (but not delNS1) infection resulted in the production of IL-15 levels ranging from 70 to 1140 pg/mL in the cell culture supernatants. The supernatants of delNS1-IL-15-infected (but not of delNS1-infected) melanoma cells induced primary human natural killer cell-mediated lysis of non-infected tumour cells. In conclusion, we constructed a novel oncolytic influenza virus that combines the oncolytic activity of delNS1 viruses with immunostimulatory properties through production of functional IL-15. Moreover, we showed that the oncolytic activity of delNS1 viruses can be enhanced in combination with cytotoxic anti-cancer drugs.
    Keywords: Research Article ; Biology ; Medicine ; Virology ; Infectious Diseases ; Molecular Biology ; Oncology ; Dermatology
    E-ISSN: 1932-6203
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  • 4
    Language: English
    In: PLoS ONE, 2011, Vol.6(5), p.e19705
    Description: Glycyrrhizin is known to exert antiviral and anti-inflammatory effects. Here, the effects of an approved parenteral glycyrrhizin preparation (Stronger Neo-Minophafen C) were investigated on highly pathogenic influenza A H5N1 virus replication, H5N1-induced apoptosis, and H5N1-induced pro-inflammatory responses in lung epithelial (A549) cells. Therapeutic glycyrrhizin concentrations substantially inhibited H5N1-induced expression of the pro-inflammatory molecules CXCL10, interleukin 6, CCL2, and CCL5 (effective glycyrrhizin concentrations 25 to 50 µg/ml) but interfered with H5N1 replication and H5N1-induced apoptosis to a lesser extent (effective glycyrrhizin concentrations 100 µg/ml or higher). Glycyrrhizin also diminished monocyte migration towards supernatants of H5N1-infected A549 cells. The mechanism by which glycyrrhizin interferes with H5N1 replication and H5N1-induced pro-inflammatory gene expression includes inhibition of H5N1-induced formation of reactive oxygen species and (in turn) reduced activation of NFκB, JNK, and p38, redox-sensitive signalling events known to be relevant for influenza A virus replication. Therefore, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease.
    Keywords: Research Article ; Medicine ; Infectious Diseases ; Pharmacology
    E-ISSN: 1932-6203
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  • 5
    Language: English
    In: Cellular and Molecular Life Sciences, 2011, Vol.68(6), pp.1079-1090
    Description: Human cytomegalovirus (HCMV) is a major pathogen in immunocompromised individuals. Here, non-toxic concentrations of the anti-cancer kinase inhibitor sorafenib were shown to inhibit replication of different HCMV strains (including a ganciclovir-resistant strain) in different cell types. In contrast to established anti-HCMV drugs, sorafenib inhibited HCMV major immediate early promoter activity and HCMV immediate early antigen (IEA) expression. Sorafenib is known to inhibit Raf. Comparison of sorafenib with the MEK inhibitor U0126 suggested that sorafenib inhibits HCMV IEA expression through inhibition of Raf but independently of signaling through the Raf downstream kinase MEK 1/2. In concordance, siRNA-mediated depletion of Raf but not of MEK-reduced IEA expression. In conclusion, sorafenib diminished HCMV replication in clinically relevant concentrations and inhibited HCMV IEA expression, a pathophysiologically relevant event that is not affected by established anti-HCMV drugs. Moreover, we demonstrated for the first time that Raf activation is involved in HCMV IEA expression.
    Keywords: Human cytomegalovirus ; Sorafenib ; Kinase inhibitor ; Raf ; Immediate early antigen ; Cancer chemotherapy ; Oncomodulation ; Antiviral therapy
    ISSN: 1420-682X
    E-ISSN: 1420-9071
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  • 6
    Language: English
    In: Medical Microbiology and Immunology, 2014, Vol.203(6), pp.365-371
    Description: Vaccination has proven to be one of the best weapons protecting the mankind against infectious diseases. Along with the huge progress in microbiology, numerous highly efficacious and safe vaccines have been produced by conventional technology (cultivation), by the use of molecular biology (genetic modification), or by synthetic chemistry. Sterilising prevention is achieved by the stimulation of antibody production, while the stimulation of cell-mediated immune responses may prevent the outbreak of disease in consequence of an acute or reactivated infection. From several examples, two rules are deduced to evaluate the perspectives of future vaccine developments: They are promising, if (1) the natural infectious disease induces immunity or (2) passive immunisation (transfer of antibodies, adoptive transfer of lymphocytes) is successful in preventing infection.
    Keywords: Vaccines ; Passive immunisation ; Adoptive transfer of lymphocytes ; Hepatitis virus ; Influenza virus ; Herpes viruses ; HIV ; Tuberculosis ; Diphtheria ; Tetanus ; Oncogenic HPV
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 7
    Language: English
    In: Phytomedicine, 2011, Vol.18(5), pp.384-386
    Description: The extract EPs 7630 is an approved drug for the treatment of acute bronchitis in Germany. The postulated mechanisms underlying beneficial effects of EPs 7630 in bronchitis patients include immunomodulatory and cytoprotective effects, inhibition of interaction between bacteria and host cells, and increase of cilliary beat frequency on respiratory cells. Here, we investigated the influence of EPs 7630 on replication of a panel of respiratory viruses. Determination of virus-induced cytopathogenic effects and virus titres revealed that EPs 7630 at concentrations up to 100 μg/ml interfered with replication of seasonal influenza A virus strains (H1N1, H3N2), respiratory syncytial virus, human coronavirus, parainfluenza virus, and coxsackie virus but did not affect replication of highly pathogenic avian influenza A virus (H5N1), adenovirus, or rhinovirus. Therefore, antiviral effects may contribute to the beneficial effects exerted by EPs 7630 in acute bronchitis patients.
    Keywords: Pelargonium Sidoides ; Respiratory Viruses ; Acute Bronchitis ; Medicine ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0944-7113
    E-ISSN: 1618-095X
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  • 8
    Language: English
    In: Trends in Molecular Medicine, 2004, Vol.10(1), pp.19-23
    Description: Recently, the term oncomodulation has been proposed to express the ability of human cytomegalovirus (HCMV) to modify tumor cell biology, a phenomenon that is independent from transformation. Because past studies have failed to show that HCMV can transform normal human cells, HCMV has not been regarded as an oncogenic tumor virus. However, recent investigations have revealed a high frequency of HCMV in tumor cells of malignancies such as colon cancer, malignant glioma, prostatic intraepithelial neoplasia, and carcinoma. Data from experiments with HCMV-infected tumor cell lines have highlighted the oncomodulatory potential of HCMV and provided important insights into the patho- mechanisms associated with aberrant signaling pathways and transcription factor and/or tumor suppressor function of the host cell.
    Keywords: Medicine ; Biology
    ISSN: 1471-4914
    E-ISSN: 1471-499X
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  • 9
    Language: English
    In: LaboratoriumsMedizin / Journal of Laboratory Medicine, Sept 1, 2010, Vol.34(5), p.257(4)
    Description: A variety of factors are known to influence qualitative and quantitative serological assays. Here, we discuss such pitfalls in serology emerging in a case of influenza A/H1N1v-hemagglutination inhibition test (H1N1-HHT) subsequent to hyposensitization and vaccinations. Assuming that hyposensitization and vaccinations are frequently provided services, their potential interference with serological assays should be considered. Keywords: disturbing factors in serodiagnosis; H1N1; hyposensitization; vaccination. Qualitative und quantitative serologische Verfahren konnen durch Interferenzen gestort sein. Wir konnten in einem exemplarischen Fall anhand des Influenza A/H1N1v-Hamagglutinationshemmtests (H1N1-HHT) zeigen, dass auch Hyposensibilisierungstherapie und Vakzination zu Interaktionen in der serologischen Diagnostik fuhren und die Aussagekraft des H1N1-HHT massiv beeintrachtigen. Vor dem Hintergrund, dass Hyposensibilisierung und Vakzination im Klinik- und Praxisalltag haufig erbrachte Leistungen darstellen, erscheint dieser Umstand berichtenswert. Schlusselworter: H1N1; Hyposensibilisierung; Storfaktoren in der serologischen Diagnostik; Vakzination.
    ISSN: 0342-3026
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  • 10
    Language: English
    In: Medical Microbiology and Immunology, 2018, Vol.207(5), pp.249-253
    Description: Several virus infections affect the pregnancy itself as well as the foetal development (rubella, PVB19, VZV, HSV, HCMV, HBV, HIV). Prevention can be established by vaccination or an assessment of the immunity status as well as by chemotherapy. The following review provides an update to current aspects focusing on the role of serologic screening.
    Keywords: Pregnancy ; Vertical virus infections ; Serologic screening
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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