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Berlin Brandenburg

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  • 1
    Language: English
    In: BBA - Reviews on Cancer, August 2014, Vol.1846(1), pp.121-129
    Description: Immunodeficiency is a severe side effect of radiation therapy, notably at high radiation doses. It may also impact healthy individuals exposed to environmental ionizing radiation. Although it is believed to result from cytotoxicity of bone marrow cells and of immunocompetent cells in the peripheral blood, the response of distinct bone marrow and blood cell subpopulations following exposure to ionizing radiation is not yet fully explored. In this review, we aim to compile the knowledge on radiation sensitivity of immunocompetent cells and to summarize data from bone marrow and peripheral blood cells derived from mouse and human origin. In addition, we address the radiation response of blood stem and progenitor cells. The data indicate that stem cells, T helper cells, cytotoxic T cells, monocytes, neutrophils and, at a high degree, B cells display a radiation sensitive phenotype while regulatory T cells, macrophages, dendritic cells and natural killer cells appear to be more radioresistant. No conclusive data are available for basophil and eosinophil granulocytes. Erythrocytes and thrombocytes, but not their precursors, seem to be highly radioresistant. Overall, the data indicate considerable differences in radiosensitivity of bone marrow and blood normal and malignant cell populations, which are discussed in the light of differential radiation responses resulting in hematotoxicity and related clinical implications.
    Keywords: Radiation ; Cancer Therapy ; DNA Repair ; Lymphocytes ; Monocytes ; Stem Cells ; Biology ; Chemistry
    ISSN: 0304-419X
    E-ISSN: 1879-2561
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  • 2
    Language: English
    In: Cancer Research, 04/15/2013, Vol.73(8 Supplement), pp.4687-4687
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
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  • 3
    In: Annals of the New York Academy of Sciences, October 2010, Vol.12091(1), pp.109-117
    Description: Joint application of standard tumor therapies like radiotherapy and/or chemotherapy with immune therapy has long been considered not to fit. However, it has become accepted that immune responses may contribute to the elimination of cancer cells. We present how –induced tumor cell death by irradiation, chemotherapeutic agents, or hyperthermia can be rendered more immunogenic. High hydrostatic pressure is introduced as an innovative inactivation method for tumor cells used as vaccines. Annexin A5, being a natural occurring ligand for phosphatidylserine that is exposed by dying tumor cells, renders apoptotic tumor cells immunogenic and induces tumor regression. Combinations of irradiation with hyperthermia may also foster antitumor responses. For preparation of autologous tumor cell vaccines, high hydrostatic pressure is suitable to induce immunogenic cancer cell death. Future work will be aimed toward evaluating which combination and chronological sequence of radiotherapy, chemotherapy, hyperthermia, annexin A5, and/or autologous tumor cell vaccines will induce specific and long‐lasting antitumor immunity.
    Keywords: Dead Tumor Cells ; Immune Modulation ; Autologous Vaccine ; High Hydrostatic Pressure ; Annexin A5 ; Hyperthermia
    ISSN: 0077-8923
    E-ISSN: 1749-6632
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  • 4
    Language: English
    In: Journal of Controlled Release, 28 November 2013, Vol.172(1), pp.201-206
    Description: Nanoparticles (NP) as carriers for anti-cancer drugs have shown great promise. Specific targeting of NP to malignant cells, however, remains an unsolved problem. Conjugation of antibodies specific for tumor membrane antigens to NP represents one approach to improve specificity and to increase therapeutic efficacy. In the present study, for the first time a novel membrane heat shock protein (Hsp70)-specific antibody (cmHsp70.1) was coupled to human serum albumin (HSA) NP, loaded with microRNA (miRNA) plasmids to target the inhibitor of apoptosis protein survivin. The physicochemical properties of monodisperse miRNA-loaded NP showed a diameter of 180 nm to 220 nm, a plasmid incorporation of more than 95% and a surface binding capacity of the antibody of 70–80%. Antibody-conjugated NP displayed an increased cellular uptake in U87MG and LN229 glioblastoma cells compared to isotype control antibody, PEG-coupled controls and peripheral blood lymphocytes (PBL). Survivin expression was significantly reduced in cells treated with the Hsp70-miRNA-NP as compared to non-conjugated NP. Hsp70-miRNA-NP enhanced radiation-induced increase in caspase 3/7 activity and decrease in clonogenic cell survival. In summary, cmHsp70.1 miRNA-NP comprise an enhanced tumor cell uptake and increased therapeutic efficacy of radiation therapy and provide the basis for the development of antibody-based advanced carrier systems for a tumor cell specific targeting. Treatment of glioma cells with cmHsp70.1 antibody coated and survivin miRNA plasmid loaded NP enhances cellular uptake, attenuates survivin expression and decreases survival indicating an increased therapeutic effectiveness of irradiation.
    Keywords: HSA Nanoparticles ; Expression Plasmids ; RNA Interference ; Survivin ; Radiosensitization ; Glioblastoma ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0168-3659
    E-ISSN: 1873-4995
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  • 5
    Language: English
    In: International Journal of Radiation Oncology, Biology, Physics, 15 July 2013, Vol.86(4), pp.785-790
    Description: To examine whether nuclear NF-κB expression correlates with outcome in patients with head and neck squamous cell carcinoma (HNSCC) treated with primary chemoradiation therapy (CRT). Between 2007 and 2010, 101 patients with locally advanced primary HNSCC were treated with definitive simultaneous CRT. Pretreatment biopsy specimens were analyzed for NF-κB p65 (RelA) nuclear immunoreactivity. A sample was assigned to be positive with more than 5% positive nuclear expression. The predictive relevance of NF-κB and clinicopathologic factors for overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS), and metastasis-free survival (DMFS) was examined by univariate and multivariate analysis. No significant differences between the groups were observed with regard to age, sex, total radiation dose, fractionation mode, total chemotherapy applied, T stage or grading. Patients with p65 nuclear positive biopsy specimens showed significantly a higher rate of lymph node metastasis (cN2c or cN3 status, =.034). Within a mean follow-up time of 25 months (range, 2.33-62.96 months) OS, PFS, and DMFS were significantly poorer in the p65 nuclear positive group ( =.008, =.027, and =.008, respectively). These correlations remained significant in multivariate analysis. NF-κB/p65 nuclear expression is associated with increased lymphatic and hematogenous tumor dissemination and decreased survival in HNSCC patients treated with primary CRT. Our results may foster further investigation of a predictive relevance of NF-κB/p65 and its role as a suitable target for a molecular-based targeted therapy in HNSCC cancer.
    Keywords: Medicine
    ISSN: 0360-3016
    E-ISSN: 1879-355X
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  • 6
    Language: English
    In: International Journal of Radiation Oncology, Biology, Physics, 01 August 2013, Vol.86(5), pp.901-907
    Description: To investigate the prognostic value of epidermal growth factor receptor (EGFR) expression in pretreatment tumor biopsy specimens of patients with anal cancer treated with concurrent 5-fluorouracil and mitomycin C-based chemoradiation therapy (CRT). Immunohistochemical staining for EGFR was performed in pretreatment biopsy specimens of 103 patients with anal carcinoma. EGFR expression was correlated with clinical and histopathologic characteristics and with clinical endpoints, including local failure-free survival (LFFS), colostomy-free survival (CFS), distant metastases-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS). EGFR staining intensity was absent in 3%, weak in 23%, intermediate in 36% and intense in 38% of the patients. In univariate analysis, the level of EGFR staining was significantly correlated with CSS (absent/weak vs intermediate/intense expression: 5-year CSS, 70% vs 86%, =.03). As a trend, this was also observed for DMFS (70% vs 86%, =.06) and LFFS (70% vs 87%, =.16). In multivariate analysis, N stage, tumor differentiation, and patients’ sex were independent prognostic factors for CSS, whereas EGFR expression only reached borderline significance (hazard ratio 2.75; =.08). Our results suggest that elevated levels of pretreatment EGFR expression could be correlated with favorable clinical outcome in anal cancer patients treated with CRT. Further studies are warranted to elucidate how EGFR is involved in the response to CRT.
    Keywords: Medicine
    ISSN: 0360-3016
    E-ISSN: 1879-355X
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  • 7
    In: Translational Cancer Research, 04/2016, Vol.5(2), pp.199-202
    ISSN: 2218676X
    E-ISSN: 22196803
    Source: CrossRef
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  • 8
    Language: English
    In: BBA - Reviews on Cancer, August 2015, Vol.1856(1), pp.130-143
    Description: Radiation therapy is one of the most commonly used non-surgical interventions in tumor treatment and is often combined with other modalities to enhance its efficacy. Despite recent advances in radiation oncology, treatment responses, however, vary considerably between individual patients. A variety of approaches have been developed to enhance radiation response or to counteract resistance to ionizing radiation. Among them, a relatively novel class of radiation sensitizers comprises nanoparticles (NPs) which are highly efficient and selective systems in the nanometer range. NPs can either encapsulate radiation sensitizing agents, thereby protecting them from degradation, or sensitize cancer cells to ionizing radiation via their physicochemical properties, e.g. high Z number. Moreover, they can be chemically modified for active molecular targeting and the imaging of tumors. In this review we will focus on recent developments in nanotechnology, different classes and modifications of NPs and their radiation sensitizing properties.
    Keywords: Nanotechnology ; Nanoparticles ; Radiation Therapy ; Radiation Sensitization ; Cancer Therapy ; Molecular Tumor Targeting ; Biology ; Chemistry
    ISSN: 0304-419X
    E-ISSN: 1879-2561
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  • 9
    Language: English
    In: Annals of the Rheumatic Diseases, 21 December 2018
    Description: It is estimated that 24% of the general adult population is currently suffering from osteoarthritis (OA), affecting 10% of men and 18% of women over 60 years of age in high-income countries. A WHO report predicted that degenerative OA will become the fourth leading cause of disability by 2020.1 This may not only affect the individuals who suffer from the diseases, but will undeniably have an impact on national health systems in social and economic terms.
    Keywords: Osteoarthritis ; Knee Osteoarthritis ; Hand Osteoarthritis
    ISSN: 0003-4967
    ISSN: 00034967
    E-ISSN: 1468-2060
    E-ISSN: 14682060
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  • 10
    Language: English
    In: International Journal of Radiation Oncology, Biology, Physics, 2010, Vol.77(1), pp.226-234
    Description: Increased expression of survivin has been identified as a negative prognostic marker in a variety of human cancers. We have previously shown that survivin is a radiation-resistance factor and that the therapeutic effect of survivin knock-down might result from an impaired DNA repair capacity. In this study, we aimed to elucidate an interrelationship between survivin's cellular localization and DNA double-strand break repair. Survivin's cellular distribution and nuclear complex formation were assayed by Western blotting of subcellular fractions, by immunofluorescence staining, and co-immunoprecipitation in SW480 colorectal cancer cells. DNA repair capacity was analyzed by kinetics of γ-H2AX foci formation, and by DNA-dependent protein kinase (DNA-PKcs) assays in the presence of survivin-specific or nonspecific control siRNA. Following irradiation, we observed a rapid nuclear accumulation of survivin and subsequent phosphorylation of the protein in the nucleus. Co-immunoprecipitation analyses from nuclear extracts revealed an interaction among survivin, Ku70, γ-H2AX, MDC1, and DNA-PKcs that was confirmed by immunofluorescence co-localization in nuclear foci. Survivin knock down by siRNA resulted in an impaired DNA double strand break repair, as demonstrated by an increased detection of γ-H2AX foci/nucleus at 60 min and a higher amount of residual γ-H2AX foci at 24 hr postirradiation. Furthermore, we detected in survivin-depleted cells a hampered S2056 autophosphorylation of DNA-PKcs and a significantly decreased DNA-PKcs kinase activity. These data indicate that nuclear survivin is linked to DNA double-strand break repair by interaction with members of the DNA double-strand breaks repair machinery, thus regulating DNA-PKcs activity.
    Keywords: Survivin ; Colorectal Cancer ; DNA Repair ; DNA-Pkcs ; Mdc1 ; Phospho-Histone H2ax ; Medicine
    ISSN: 0360-3016
    E-ISSN: 1879-355X
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