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Berlin Brandenburg

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  • 1
    Language: English
    In: International journal of cancer, 01 May 2016, Vol.138(9), pp.2231-46
    Description: The metabolic properties of lymphomas derived from germinal center (GC) B cells have important implications for therapeutic strategies. In this study, we have compared metabolic features of Hodgkin-Reed-Sternberg (HRS) cells, the tumor cells of classical Hodgkin's lymphoma (cHL), one of the most frequent (post-)GC-derived B-cell lymphomas, with their normal GC B cell counterparts. We found that the ratio of oxidative to nonoxidative energy conversion was clearly shifted toward oxidative phosphorylation (OXPHOS)-linked ATP synthesis in HRS cells as compared to GC B cells. Mitochondrial mass, the expression of numerous key proteins of oxidative metabolism and markers of mitochondrial biogenesis were markedly upregulated in cHL cell lines and in primary cHL cases. NFkappaB promoted this shift to OXPHOS. Functional analysis indicated that both cell growth and viability of HRS cells depended on OXPHOS. The high rates of OXPHOS correlated with an almost complete lack of lactate production in HRS cells not observed in other GC B-cell lymphoma cell lines. Overall, we conclude that OXPHOS dominates energy conversion in HRS cells, while nonoxidative ATP production plays a subordinate role. Our results suggest that OXPHOS could be a new therapeutic target and may provide an avenue toward new treatment strategies in cHL.
    Keywords: Classical Hodgkin Lymphoma ; Energy Metabolism ; Oxidative Phosphorylation ; Oxidative Phosphorylation ; Hodgkin Disease -- Metabolism ; Reed-Sternberg Cells -- Metabolism
    ISSN: 00207136
    E-ISSN: 1097-0215
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  • 2
    In: International Journal of Cancer, 01 May 2016, Vol.138(9), pp.2231-2246
    Description: The metabolic properties of lymphomas derived from germinal center (GC) B cells have important implications for therapeutic strategies. In this study, we have compared metabolic features of Hodgkin–Reed–Sternberg (HRS) cells, the tumor cells of classical Hodgkin's lymphoma (cHL), one of the most frequent (post‐)GC‐derived B‐cell lymphomas, with their normal GC B cell counterparts. We found that the ratio of oxidative to nonoxidative energy conversion was clearly shifted toward oxidative phosphorylation (OXPHOS)‐linked ATP synthesis in HRS cells as compared to GC B cells. Mitochondrial mass, the expression of numerous key proteins of oxidative metabolism and markers of mitochondrial biogenesis were markedly upregulated in cHL cell lines and in primary cHL cases. NFkappaB promoted this shift to OXPHOS. Functional analysis indicated that both cell growth and viability of HRS cells depended on OXPHOS. The high rates of OXPHOS correlated with an almost complete lack of lactate production in HRS cells not observed in other GC B‐cell lymphoma cell lines. Overall, we conclude that OXPHOS dominates energy conversion in HRS cells, while nonoxidative ATP production plays a subordinate role. Our results suggest that OXPHOS could be a new therapeutic target and may provide an avenue toward new treatment strategies in cHL. What's new? The surprising revelation that Hodgkin–Reed–Sternberg cells of classical Hodgkin lymphoma (cHL) originate from postgerminal center B cells raises new questions about the metabolic properties of cHL cells and possible therapeutic implications. This study shows that in contrast to the cells of other B‐cell lymphomas, cHL cells require oxidative phosphorylation (OXPHOS)‐dependent ATP synthesis for cell survival and cell growth, rendering them susceptible to OXPHOS inhibition. The results could inform the advance of novel therapeutic strategies in Hodgkin lymphoma.
    Keywords: Classical Hodgkin Lymphoma ; Energy Metabolism ; Oxidative Phosphorylation
    ISSN: 0020-7136
    E-ISSN: 1097-0215
    Source: John Wiley & Sons, Inc.
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  • 3
    Language: English
    In: Human Pathology, September 2013, Vol.44(9), pp.1737-1746
    Description: In nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), little is known about the presence of intranodular clusters of cytologically activated lymphoid cells producing a moth-eaten pattern histologically. This pilot study of 32 NLPHL cases from Finland ascertained (1) the frequency of the intranodular clusters of activated lymphoid cells, (2) the immunophenotype of the activated cells, (3) the size and immunophenotype of the rosetting cells, and (4) the clinical significance of the activated cells. Histologically, intranodular clusters of activated cells produced a moth-eaten pattern in 100% (32 cases; subtle in 62.5%, overt in 37.5%). In immunostains, activated cells in subtle clusters (20 cases) were very difficult to identify. Twelve cases had overt clusters of activated cells, which were positive with CD3, CD4, PD1, CXCL13 (T follicular helper [T ] phenotype), but rarely with Ki-67 and BCL2. Most activated rosetting cells had the same immunophenotype as the nonrosetting cells, except for CXCL13. Clinical presentation for all 32 Finnish patients was distinctive: 97% men, 97% with peripheral lymphadenopathy and 35.5% with stage III/IV disease. Only 22% relapsed; 97% were in remission. There was no significant clinical difference between cases with overt and subtle clusters. Intranodular activated T cells in NLPHL appeared to be nonproliferating and not long-living, and they were not associated with any adverse clinical outcome. Although most activated cells were T cells, it seemed that they were unable to increase the number of malignant cells. The pathogenetic role of the intranodular activated T and the small T cells in NLPHL needs further investigation.
    Keywords: Hodgkin Lymphoma ; Nodular Lymphocyte Predominant Hodgkin Lymphoma ; Intranodular Clusters of Activated Cells ; Activated T Cells ; T Follicular Helper Cells (Tfh) ; Pd1 ; Cxcl13 ; Rosettes ; Medicine
    ISSN: 0046-8177
    E-ISSN: 1532-8392
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  • 4
    In: Glia, November 2013, Vol.61(11), pp.1822-1831
    Description: Searching for chemical agents and molecular targets protecting against secondary neuronal damage reflects one major issue in neuroscience. Cannabinoids limit neurodegeneration by activation of neuronal G protein‐coupled cannabinoid receptor 1 (CB) and microglial G protein‐coupled cannabinoid receptor 2 (CB). However, pharmacological experiments with CB/CB‐deficient mice unraveled the existence of further, so‐called non‐CB/non‐CB G protein‐coupled receptor (GPR) subtypes. GPR55, whose function in the brain is still poorly understood, represents a novel target for various cannabinoids. Here, we investigated whether GPR55 reflects a potential beneficial target in neurodegeneration by using the excitotoxicity model of rat organotypic hippocampal slice cultures (OHSC). ‐α‐Lysophosphatidylinositol (LPI), so far representing the most selective agonist for GPR55, protected dentate gyrus granule cells and reduced the number of activated microglia after NMDA (50 µM) induced lesions. The relevance of GPR55 activation for LPI‐mediated neuroprotection was determined by using siRNA. Microglia seems to mediate the observed neuroprotection since their depletion in OHSC attenuated the beneficial effects of LPI. Moreover, LPI alone induced microglia chemotaxis but conversely significantly attenuated ATP triggered microglia migration. These effects seemed to be independent from intracellular Ca and p38 or p44/p42 MAPK phosphorylation. In conclusion, this study unmasked a yet unknown role for GPR55 in neuroprotection driven by LPI‐mediated modulation of microglia function. GLIA 2013;61:1822–1831
    Keywords: Microglia ; Neuroprotection ; Excitotoxicity ; Organotypic Hippocampal Slice Cultures ; Cannabinoid Receptor
    ISSN: 0894-1491
    E-ISSN: 1098-1136
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  • 5
    In: JDDG: Journal der Deutschen Dermatologischen Gesellschaft, June 2015, Vol.13(6), pp.575-577
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/ddg.12567/abstract Byline: Igor Hrgovic, Ria Winkelmann, Thomas Joseph Vogl, Michael Wagner, Hanan El Youzouri, Roland Kaufmann, Markus Meissner ***** No abstract is available for this article. *****
    ISSN: 1610-0379
    E-ISSN: 1610-0387
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  • 6
    Language: English
    In: Archives of Gynecology and Obstetrics, 2018, Vol.298(5), pp.945-950
    Description: To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s00404-018-4887-1 Byline: Khayal Gasimli (1), Martina Straussner (1), Iryna Schmeil (1), Thomas Karn (1), Ria Winkelmann (2), Sven Becker (1), Ahmed El-Balat (1) Keywords: Squamous cell carcinoma of vulva; Re-excision of adjacent VIN III; Histological tumour-free margin; Vulvar intraepithelial neoplasia (VIN III); Disease-free survival Abstract: Background hTFM in primary vulvar cancer is an important prognostic factor. Ideally, a diameter of〉8 mm should be achieved after primary surgery. The role of VIN III persistence after primary surgery in vulvar cancer is still unclear. The main objective of the current study was to study the role of residual VIN III re-excision and compare differences in disease-free survival among patients with different hTFM and in primary vulvar cancer. Methods Forty-two patients with residual adjacent VIN III after primary surgery for vulvar cancer which were operated between 2000 and 2016 in our clinic were enrolled in this retrospective study. Re-excision rates for residual adjacent VIN III were calculated. According to the histological margin patients were divided into three group:〈3, 3--8 and〉8 mm. Univariate and multivariate analyses were conducted using the Kaplan--Meier method and Cox proportional hazards models, respectively. Results The vast majority of patients had pT1b stage (57.1%), grading G2 (71.4%) and lymph node-negative (45.3%) disease at first diagnosis. The re-excision rate was 57.1%. The 5-year disease-free survival (DFS) rates in patients with〈3, 3--8 and〉8 mm hTFM were 50.0, 50.0 and 81.0%, respectively (p=0.032). The 5-year DFS rates in patients with re-excision and without re-excision for VIN III were 77.3 and 52.9%, respectively (p=0.060). In univariate analysis was solely hTFM〉8 mm a prognostic factor for DFS (p=0.017). Conclusions hTFM may be a potential prognostic indicator for DFS in vulvar cancer patients. Re-excision for residual adjacent VIN III could not be established as a prognostic factor for DFS after primary surgery in squamous cell cancer of vulva. Author Affiliation: (1) 0000 0004 1936 9721, grid.7839.5, Department of Obstetrics and Gynecology, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany (2) Dr. Senckenberg Institute of Pathology, Frankfurt, Germany Article History: Registration Date: 25/08/2018 Received Date: 13/05/2018 Accepted Date: 24/08/2018 Online Date: 06/09/2018 Article note: Khayal Gasimli and Martina Straussner authors contributed equally to this study.
    Keywords: Squamous cell carcinoma of vulva ; Re-excision of adjacent VIN III ; Histological tumour-free margin ; Vulvar intraepithelial neoplasia (VIN III) ; Disease-free survival
    ISSN: 0932-0067
    E-ISSN: 1432-0711
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  • 7
    In: JDDG: Journal der Deutschen Dermatologischen Gesellschaft, February 2018, Vol.16(2), pp.208-210
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/ddg.13422/abstract Byline: Manuel Jager, Ria Winkelmann, Kathrin Eichler, Eva Valesky, Roland Kaufmann, Markus Meissner ***** No abstract is available for this article. *****
    Keywords: Lipoma;
    ISSN: 1610-0379
    E-ISSN: 1610-0387
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  • 8
    In: JDDG: Journal der Deutschen Dermatologischen Gesellschaft, February 2018, Vol.16(2), pp.207-209
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/ddg.13422_g/abstract Byline: Manuel Jager, Ria Winkelmann, Kathrin Eichler, Eva Valesky, Roland Kaufmann, Markus Meissner ***** No abstract is available for this article. *****
    ISSN: 1610-0379
    E-ISSN: 1610-0387
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  • 9
    In: JDDG: Journal der Deutschen Dermatologischen Gesellschaft, June 2015, Vol.13(6), pp.575-577
    ISSN: 1610-0379
    ISSN: JDDG: Journal der Deutschen Dermatologischen Gesellschaft
    E-ISSN: 1610-0387
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  • 10
    Language: English
    In: Cancer Treatment Reviews, April 2018, Vol.65, pp.11-21
    Description: Anal squamous cell carcinoma (ASCC) is associated with infection with high-risk strains of human papilloma virus (HPV) in 70–90% of cases and a rise in incidence has been observed in the last decades. Definitive chemoradiotherapy (CRT) using 5-fluorouracil and mitomycin C constitutes the standard treatment for localized disease, but about 30% of patients do not respond or relapse locally. Phase I/II trials testing targeted agents, such as epidermal-growth-factor receptor (EGFR) inhibitors, have failed to improve clinical outcome and resulted in increased toxicities. Modern imaging methods and biomarkers, also in the context of HPV status, should be further explored to improve patient stratification. In the present review, we will discuss the current clinical evidence and future perspectives in the management of ASCC. HPV-positive ASCC is more immunogenic with a higher density of tumor infiltrating lymphocytes that correlate with better response to CRT and more favorable prognosis compared to HPV-negative tumors. Immunotherapies including immune checkpoint inhibitors have brought new hope and promising results were recently demonstrated in metastatic ASCC. The addition of immunotherapies to CRT for localized disease is tested in early phase trials, and these results could have a profound impact on the way we treat ASCC in near future. Further research and novel approaches are expected to enhance our understanding of tumor biology and immunology, and improve patient stratification and treatment adaptation in the context of personalized medicine.
    Keywords: Anal Cancer ; Clinical Trials ; Imaging ; Imrt ; Chemoradiotherapy ; Immunotherapy ; Medicine
    ISSN: 0305-7372
    E-ISSN: 1532-1967
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