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Berlin Brandenburg

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  • 1
    Language: English
    In: Nucleic acids research, 2014, Vol.42(17), pp.11040-55
    Description: Histone methylation changes and formation of chromatin loops involving enhancers, promoters and 3' end regions of genes have been variously associated with active transcription in eukaryotes. We have studied the effect of activation of the retinoic A receptor, at the RARE-promoter chromatin of CASP9 and CYP26A1 genes, 15 and 45 min following RA exposure, and we found that histone H3 lysines 4 and 9 are demethylated by the lysine-specific demethylase, LSD1 and by the JMJ-domain containing demethylase, D2A. The action of the oxidase (LSD1) and a dioxygenase (JMJD2A) in the presence of Fe++ elicits an oxidation wave that locally modifies the DNA and recruits the enzymes involved in base and nucleotide excision repair (BER and NER). These events are essential for the formation of chromatin loop(s) that juxtapose the RARE element with the 5' transcription start site and the 3' end of the genes. The RARE bound-receptor governs the 5' and 3' end selection and directs the productive transcription cycle of RNA polymerase. These data mechanistically link chromatin loops, histone methylation changes and localized DNA repair with transcription.
    Keywords: Histone Code ; Transcription, Genetic ; Chromatin -- Chemistry ; Tretinoin -- Pharmacology
    ISSN: 03051048
    E-ISSN: 1362-4962
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  • 2
    Language: English
    In: PLoS ONE, 2012, Vol.7(4), p.e34405
    Description: Dual Oxidases (DUOX) 1 and 2 are efficiently expressed in thyroid, gut, lung and immune system. The function and the regulation of these enzymes in mammals are still largely unknown. We report here that DUOX 1 and 2 are expressed in human neuroblastoma SK-N-BE cells as well as in a human oligodendrocyte cell line (MO3-13) and in rat brain and they are induced by platelet derived growth factor (PDGF). The levels of DUOX 1 and 2 proteins and mRNAs are induced by reactive oxygen species (ROS) produced by the membrane NADPH oxidase. As to the mechanism, we find that PDGF stimulates membrane NADPH oxidase to produce ROS, which stabilize DUOX1 and 2 mRNAs and increases the levels of the proteins. Silencing of gp91 phox (NOX2), or of the other membrane subunit of NADPH oxidase, p22 phox , blocks PDGF induction of DUOX1 and 2. These data unravel a novel mechanism of regulation of DUOX enzymes by ROS and identify a circuitry linking NADPH oxidase activity to DUOX1 and 2 levels in neuroblastoma cells.
    Keywords: Research Article ; Biology ; Neuroscience
    E-ISSN: 1932-6203
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  • 3
    Language: English
    In: Gastric Cancer, 2014, Vol.17(1), pp.107-115
    Description: Byline: Carmine Fedele (1), Silvia Carvalho (2,3,4), Gennaro Riccio (1), Rolando Paciello (1), Paolo Laccetti (1,5), Fernando Schmitt (2,3), Claudia De Lorenzo (1,6,7) Keywords: Immunotherapy; ErbB2/Her2; Gastric cancer; Trastuzumab Abstract: Background Gastric cancer represents one of the most common causes of cancer deaths worldwide. Overexpression of ErbB2, a tyrosine kinase receptor involved in the pathogenesis of several human cancer types, has been reported also in gastric cancer. Thus, the inhibition of ErbB2 signal transduction pathways by the use of human antibodies could be a valuable strategy for the therapy of this type of cancer. Methods We tested for the first time the antitumor effects on gastric cancer cells of Erb-hcAb, a novel fully human compact antibody, prepared in our laboratory, which targets a different epitope of ErbB2 with respect to trastuzumab, the only anti-ErbB2 antibody currently in clinical use for both breast and gastric cancer therapy. Results Herein we demonstrate that the in vitro and in vivo growth of gastric cancer cells is efficiently inhibited by Erb-hcAb, which shows antitumor effects on the NCI-N87 cell line more potent than those observed for trastuzumab. Conclusions Erb-hcAb could be a promising candidate in the immunotherapy of gastric cancer as it combines the antiproliferative effect associated with the inhibition of ErbB2 signaling on tumor target cells with the ability to induce antibody-dependent cellular cytotoxicity. Author Affiliation: (1) Dipartimento di Biologia Strutturale e Funzionale, Universita di Napoli Federico II, via Cinthia, 80126, Naples, Italy (2) Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal (3) Medical Faculty, University of Porto, Porto, Portugal (4) Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel (5) Dipartimento di Biologia, Universita di Napoli Federico II, Naples, Italy (6) Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universita di Napoli Federico II, Naples, Italy (7) CEINGE Biotecnologie avanzate, via Gaetano Salvatore 486, 80145, Naples, Italy Article History: Registration Date: 14/02/2013 Received Date: 10/10/2012 Accepted Date: 11/02/2013 Online Date: 05/03/2013
    Keywords: Immunotherapy ; ErbB2/Her2 ; Gastric cancer ; Trastuzumab
    ISSN: 1436-3291
    E-ISSN: 1436-3305
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  • 4
    Language: English
    In: Investigational New Drugs, 2010, Vol.28(2), pp.115-123
    Description: The active components of Cannabis sativa and their derivatives produce a wide spectrum of effects, some of which may have clinical application. The discovery of specific cannabinoid receptors and a family of endogenous ligands of those receptors has attracted much attention to cannabinoids as agents capable of controlling the decision of cells to survive or die. We analysed the effects exerted by 2-methyl-2′-F-anandamide (Met-F-AEA), a metabolically stable analogue of anandamide, and observed a growth inhibition in cell lines derived from thyroid carcinomas. Growth inhibition was associated with a high level of CB1 receptor expression, suggesting that the cytotoxic effect is due to interaction with the CB1 receptor. This phenomenon was associated with activation of the protein, p53, an increased apoptotic rate, and expression of p21 CIP1/WAF1 . This study provides new insights into the mechanism of Met-F-AEA action, and could have significance in providing a basis for the management of thyroid carcinoma.
    Keywords: Apoptosis ; CB1 receptor ; Met-F-AEA ; Human thyroid carcinoma
    ISSN: 0167-6997
    E-ISSN: 1573-0646
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  • 5
    Language: English
    In: Oncology Reports, July 2012, Vol.28(1), pp.297-302
    Description: Prostate cancer is the most commonly diagnosed malignancy in men in developed countries. ErbB2, a tyrosine kinase receptor overexpressed in many human cancer types, contributes to prostate cancer progression by activating the androgen receptor in a steroid poor environment, thus promoting androgen-independent cell growth. The consequent development of hormone refractory tumors is a major obstacle in prostate cancer therapy. The inhibition of ErbB2 signal transduction pathways by the use of human antibodies could be a valuable alternative strategy for cancer therapy. We performed a comparative analysis in vitro and in vivo of the antitumor effects of three different antibodies targeting different epitopes of ErbB2: Herceptin (trastuzumab), 2C4 (pertuzumab) and Erb-hcAb (human anti-ErbB2-compact antibody), a novel fully human compact antibody produced in our laboratory. Herein, we demonstrate that the growth of both androgen-dependent and independent prostate cancer cells was efficiently inhibited by Erb-hcAb. The antitumor effects induced by Erb-hcAb on some cell lines were more potent than those observed for either Herceptin or 2C4. Thus, Erb-hcAb could be a promising candidate in the immunotherapy of prostate cancer for which no obvious treatment has been reported so far.
    Keywords: Antibodies, Monoclonal, Humanized -- Pharmacology ; Antineoplastic Agents -- Pharmacology ; Prostatic Neoplasms -- Drug Therapy ; Recombinant Fusion Proteins -- Pharmacology;
    ISSN: 1021-335X
    E-ISSN: 17912431
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  • 6
    Language: English
    In: Journal of Natural History, 30 April 2015, Vol.49(21-24), pp.1457-1475
    Description: This study focused on the morphological and functional characterization of the haemocytes from Octopus vulgaris as the first agents responsible for innate immunity. Three major haemocytes types were identified by light microscopy based on nucleus/cytoplasm ratio and the presence or absence...
    Keywords: Octopus Vulgaris ; Primary Culture ; Haemocytes ; Antimicrobial Activity ; Biology
    ISSN: 0022-2933
    E-ISSN: 1464-5262
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  • 7
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 16 July 1999, Vol.96(14), pp.7768-7773
    Description: Monomeric human pancreatic RNase, devoid of any biological activity other than its RNA degrading ability, was engineered into a dimeric protein with a cytotoxic action on mouse and human tumor cells, but lacking any appreciable toxicity on mouse and human normal cells. This dimeric variant of human pancreas RNase selectively sensitizes to apoptotic death cells derived from a human thyroid tumor. Because of its selectivity for tumor cells, and because of its human origin, this protein represents a potentially very attractive, novel tool for anticancer therapy.
    Keywords: Biological sciences -- Biology -- Cytology ; Biological sciences -- Biology -- Cytology ; Physical sciences -- Chemistry -- Chemical compounds ; Biological sciences -- Biology -- Cytology ; Health sciences -- Medical conditions -- Diseases ; Biological sciences -- Biology -- Genetics ; Health sciences -- Medical conditions -- Diseases ; Biological sciences -- Biology -- Cytology ; Physical sciences -- Physics -- Microphysics ; Biological sciences -- Biology -- Cytology
    ISSN: 00278424
    E-ISSN: 10916490
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  • 8
    Language: English
    In: Photomedicine and laser surgery, August 2010, Vol.28 Suppl 1, pp.S97-103
    Description: Noninvasive in vivo imaging of human tumors implanted in mice provides a reliable and economic tool for the investigation of tumor progression and metastasis and of the effectiveness of the antiblastic drugs on them. The purpose of this study is to report on the performance achievable by the well-known and extensively investigated HP-FRI (HematoPorphyrin (HP)-mediated Fluorescence Reflectance Imaging) when a high-quality image-acquisition device is used. Previous articles of ours showed that HP-FRI still represents a useful, simple and reliable optical imaging technique to detect surface tumors. Therefore, it is particularly suitable to be used in combination with other imaging modalities in a multimodal imaging system endowed with diagnostic capabilities much better than each separate modality. Six-week-old Crl:CD-1 nude mice were subcutaneously inoculated with tumor cells. Tumor-bearing mice were irradiated in vivo by a frequency-doubled pulsed Nd:YAG laser (lambda = 532 nm). A cooled CCD digital camera recorded fluorescence light emitted by HP injected in mice through a cut-on long-wavelength pass filter. The system we developed allows in vivo imaging of surface tumors on small animals with a large field of view, high photometric sensitivity, adequate space resolution, and short measurement time. The estimated spatial resolution is 730 microm for a fluorescence source placed about 0.5 mm under the mouse skin. The first exploration of the capabilities of this HP-FRI setup on few mice shows that it allows the detection of (a) both types of investigated tumors, (b) early stage and late stage but visually unrecognizable tumors, (c) the gross structure of tumors, and (d) the discrimination of necrotic and nonnecrotic tumor regions.
    Keywords: Hematoporphyrins ; Photosensitizing Agents ; Early Detection of Cancer -- Methods ; Neoplasms, Experimental -- Diagnosis
    ISSN: 15495418
    E-ISSN: 1557-8550
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  • 9
    In: Protein Engineering, Design & Selection, 2014, Vol. 27(3), pp.83-88
    Description: The inhibition of ErbB2 by the use of human antibodies can be a valuable strategy for the treatment of breast and gastric cancer. Trastuzumab, a humanized anti-ErbB2 antibody in clinical use, is effective but can engender resistance as well as cardiotoxicity. ImmunoRNases, made up of a human anti-ErbB2 scFv and human pancreatic ribonucleases (HP-RNases), have been engineered to overcome the limits of other immunotoxins, such as immunogenicity and nonspecific toxicity. Here, we report that a novel anti-ErbB2 immunoRNase, called Erb–HPDDADD-RNase, obtained by fusing Erbicin, a human ErbB2-directed scFv, with an HP-RNase variant that resists the cytosolic inhibitor protein, binds with high affinity to a panel of ErbB2-positive gastric tumor cells and inhibits their growth more than does the parental immunoRNase, which is not resistant to the inhibitor. Moreover, Erb–HP-DDADD-RNase is endowed with antiproliferative activity for trastuzumab-resistant cancer cells both in vitro and in vivo that is more potent than that of the parental immunoRNase. Importantly, Erb–HP-DDADD-RNase does not show cardiotoxic effects in vitro on human cardiomyocytes and does not impair cardiac function in a mouse model. Thus, Erb–HP-DDADD-RNase could fulfil the therapeutic need of cancer patients ineligible for trastuzumab treatment due to primary or acquired trastuzumab resistance or to cardiac dysfunction.
    Keywords: Breast Cancer ; Cardiotoxicity ; Erbb2 ; Gastric Cancer ; Trastuzumab - Resistance
    ISSN: 1741-0126
    E-ISSN: 1741-0134
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  • 10
    Language: English
    In: Endocrine-related cancer, June 2010, Vol.17(2), pp.373-82
    Description: Obesity is associated with an increased risk of breast cancer. A number of adipocytokines are increased in obesity causing low-level chronic inflammation associated with an increased risk of tumors. The adipocytokine leptin shows profound anti-obesity and pro-inflammatory activities. We have hypothesized that in common obesity, high circulating leptin levels might contribute to an increased risk of breast cancer by affecting mammary cell proliferation and survival. Leptin exerts its activity not only through leptin receptor (LepR), but also through crosstalk with other signaling systems implicated in tumorigenesis. In this study, we focused our attention on the relationship between the leptin/LepR axis and the estrogen receptor-alpha (ERalpha). To this aim, we utilized two human breast cancer cell lines, one ERalpha-positive cell line (MCF 7) and the other ERalpha-negative cell line (MDA-MB 231). We observed that the two cell lines had a different sensitivity to recombinant leptin (rleptin): on MCF 7 cells, rleptin induced a strong phosphorylation of the signal transducer and activator of transcription (STAT) 3 and of the extracellular related kinase 1/2 pathways with an increased cell viability and proliferation associated with an increased expression of ERalpha receptor. This response was not present in the MDA-MB 231 cells. The effects induced by leptin were lost when LepR was neutralized using either a monoclonal inhibitory antibody to LepR or LepR gene-silencing siRNA. These data suggest that there is a bidirectional communication between LepR and ERalpha, and that neutralization and/or inactivation of LepR inhibits proliferation and viability of human breast cancer cell lines. This evidence was confirmed by ex vivo studies, in which we analyzed 33 patients with breast cancer at different stages of disease, and observed that there was a statistically significant correlation between the expression of LepR and ERalpha. In conclusion, this study suggests a crosstalk between LepR and ERalpha, and could envisage novel therapeutic settings aimed at targeting the LepR in breast cancers.
    Keywords: Breast -- Metabolism ; Breast Neoplasms -- Metabolism ; Carcinoma, Ductal, Breast -- Metabolism ; Carcinoma, Lobular -- Metabolism ; Estrogen Receptor Alpha -- Metabolism ; Receptors, Leptin -- Metabolism
    ISSN: 13510088
    E-ISSN: 1479-6821
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