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  1. Article: Editorial: Cardiotoxicity induced by radiotherapy and/or chemotherapy after cancer treatment.

    Boerma, Marjan / Azimzadeh, Omid / Pasinetti, Nadia / Monceau, Virginie

    Frontiers in oncology

    2022  Volume 12, Page(s) 1087928

    Language English
    Publishing date 2022-11-22
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.1087928
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  2. Article ; Online: Introduction to the special issue on adverse outcome pathways in radiation protection.

    Chauhan, Vinita / Azimzadeh, Omid / Salomaa, Sisko / Hamada, Nobuyuki

    International journal of radiation biology

    2022  Volume 98, Issue 12, Page(s) 1691–1693

    MeSH term(s) Radiation Protection ; Adverse Outcome Pathways
    Language English
    Publishing date 2022-09-26
    Publishing country England
    Document type Editorial
    ZDB-ID 3065-x
    ISSN 1362-3095 ; 0020-7616 ; 0955-3002
    ISSN (online) 1362-3095
    ISSN 0020-7616 ; 0955-3002
    DOI 10.1080/09553002.2022.2123183
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  3. Article ; Online: Quantitative Proteomic Analysis Using Formalin-Fixed, Paraffin-Embedded (FFPE) Human Cardiac Tissue.

    Azimzadeh, Omid / Atkinson, Michael J / Tapio, Soile

    Methods in molecular biology (Clifton, N.J.)

    2021  Volume 2261, Page(s) 525–533

    Abstract: Clinical tissue archives represent an invaluable source of biological information. Formalin-fixed, paraffin-embedded (FFPE) tissue can be used for retrospective investigation of biomarkers of diseases and prognosis.Recently, the number of studies using ... ...

    Abstract Clinical tissue archives represent an invaluable source of biological information. Formalin-fixed, paraffin-embedded (FFPE) tissue can be used for retrospective investigation of biomarkers of diseases and prognosis.Recently, the number of studies using proteome profiling of samples from clinical archives has markedly increased. However, the application of conventional quantitative proteomics technologies remains a challenge mainly due to the harsh fixation process resulting in protein cross-linking and protein degradation. In the present chapter, we demonstrate a protocol for label-free proteomic analysis of FFPE tissue prepared from human cardiac autopsies. The data presented here highlight the applicability and suitability of FFPE heart tissue for understanding the molecular mechanism of cardiac injury using a proteomics approach.
    MeSH term(s) Autopsy ; Chromatography, Reverse-Phase ; Fixatives/chemistry ; Formaldehyde/chemistry ; Humans ; Myocardium/metabolism ; Paraffin Embedding ; Proteins/analysis ; Proteome ; Proteomics ; Tandem Mass Spectrometry ; Tissue Fixation
    Chemical Substances Fixatives ; Proteins ; Proteome ; Formaldehyde (1HG84L3525)
    Language English
    Publishing date 2021-01-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1186-9_33
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  4. Article ; Online: Proteomics landscape of radiation-induced cardiovascular disease: somewhere over the paradigm.

    Azimzadeh, Omid / Tapio, Soile

    Expert review of proteomics

    2017  Volume 14, Issue 11, Page(s) 987–996

    Abstract: Introduction: Epidemiological studies clearly show that thoracic or whole body exposure to ionizing radiation increases the risk of cardiac morbidity and mortality. Radiation-induced cardiovascular disease (CVD) has been intensively studied during the ... ...

    Abstract Introduction: Epidemiological studies clearly show that thoracic or whole body exposure to ionizing radiation increases the risk of cardiac morbidity and mortality. Radiation-induced cardiovascular disease (CVD) has been intensively studied during the last ten years but the underlying molecular mechanisms are still poorly understood. Areas covered: Heart proteomics is a powerful tool holding promise for the future research. The central focus of this review is to compare proteomics data on radiation-induced CVD with data arising from proteomics of healthy and diseased cardiac tissue in general. In this context we highlight common and unique features of radiation-related and other heart pathologies. Future prospects and challenges of the field are discussed. Expert commentary: Data from comprehensive cardiac proteomics have deepened the knowledge of molecular mechanisms involved in radiation-induced cardiac dysfunction. State-of-the-art proteomics has the potential to identify novel diagnostic and therapeutic markers of this disease.
    MeSH term(s) Animals ; Biomarkers ; Cardiovascular Diseases/etiology ; Cardiovascular Diseases/metabolism ; Humans ; Proteome ; Proteomics ; Radiation Injuries ; Radiation, Ionizing
    Chemical Substances Biomarkers ; Proteome
    Language English
    Publishing date 2017
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2299100-1
    ISSN 1744-8387 ; 1478-9450
    ISSN (online) 1744-8387
    ISSN 1478-9450
    DOI 10.1080/14789450.2017.1388743
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  5. Article ; Online: Radiotherapy for non-cancer diseases: benefits and long-term risks.

    Thariat, Juliette / Little, Mark P / Zablotska, Lydia B / Samson, Pamela / O'Banion, M Kerry / Leuraud, Klervi / Bergom, Carmen / Girault, Gilles / Azimzadeh, Omid / Bouffler, Simon / Hamada, Nobuyuki

    International journal of radiation biology

    2024  Volume 100, Issue 4, Page(s) 505–526

    Abstract: Purpose: The discovery of X-rays was followed by a variety of attempts to treat infectious diseases and various other non-cancer diseases with ionizing radiation, in addition to cancer. There has been a recent resurgence of interest in the use of such ... ...

    Abstract Purpose: The discovery of X-rays was followed by a variety of attempts to treat infectious diseases and various other non-cancer diseases with ionizing radiation, in addition to cancer. There has been a recent resurgence of interest in the use of such radiotherapy for non-cancer diseases. Non-cancer diseases for which use of radiotherapy has currently been proposed include refractory ventricular tachycardia, neurodegenerative diseases (e.g. Alzheimer's disease and dementia), and Coronavirus Disease 2019 (COVID-19) pneumonia, all with ongoing clinical studies that deliver radiation doses of 0.5-25 Gy in a single fraction or in multiple daily fractions. In addition to such non-cancer effects, historical indications predominantly used in some countries (e.g. Germany) include osteoarthritis and degenerative diseases of the bones and joints. This narrative review gives an overview of the biological rationale and ongoing preclinical and clinical studies for radiotherapy proposed for various non-cancer diseases, discusses the plausibility of the proposed biological rationale, and considers the long-term radiation risks of cancer and non-cancer diseases.
    Conclusions: A growing body of evidence has suggested that radiation represents a double-edged sword, not only for cancer, but also for non-cancer diseases. At present, clinical evidence has shown some beneficial effects of radiotherapy for ventricular tachycardia, but there is little or no such evidence of radiotherapy for other newly proposed non-cancer diseases (e.g. Alzheimer's disease, COVID-19 pneumonia). Patients with ventricular tachycardia and COVID-19 pneumonia have thus far been treated with radiotherapy when they are an urgent life threat with no efficient alternative treatment, but some survivors may encounter a paradoxical situation where patients were rescued by radiotherapy but then get harmed by radiotherapy. Further studies are needed to justify the clinical use of radiotherapy for non-cancer diseases, and optimize dose to diseased tissue while minimizing dose to healthy tissue.
    MeSH term(s) Humans ; Radiotherapy Dosage ; Alzheimer Disease/radiotherapy ; COVID-19/radiotherapy ; Osteoarthritis ; Tachycardia, Ventricular ; Radiotherapy/adverse effects
    Language English
    Publishing date 2024-01-05
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 3065-x
    ISSN 1362-3095 ; 0020-7616 ; 0955-3002
    ISSN (online) 1362-3095
    ISSN 0020-7616 ; 0955-3002
    DOI 10.1080/09553002.2023.2295966
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  6. Article ; Online: Irradiated Triple-Negative Breast Cancer Co-Culture Produces a Less Oncogenic Extracellular Matrix.

    Brett, Elizabeth / Rosemann, Michael / Azimzadeh, Omid / Pagani, Andrea / Prahm, Cosima / Daigeler, Adrien / Duscher, Dominik / Kolbenschlag, Jonas

    International journal of molecular sciences

    2022  Volume 23, Issue 15

    Abstract: Triple-negative breast cancer is the most common and most deadly cancer among women. Radiation is a mainstay of treatment, administered after surgery, and used in the hope that any remaining cancer cells will be destroyed. While the cancer cell response ... ...

    Abstract Triple-negative breast cancer is the most common and most deadly cancer among women. Radiation is a mainstay of treatment, administered after surgery, and used in the hope that any remaining cancer cells will be destroyed. While the cancer cell response is normally the focus of radiation therapy, little is known about the tumor microenvironment response after irradiation. It is widely reported that increased collagen expression and deposition are associated with cancer progression and poor prognosis in breast cancer patients. Aside from the classical fibrotic response, ratios of collagen isoforms have not been studied in a radiated tumor microenvironment. Here, we created one healthy co-culture of stromal fibroblasts and adipose-derived stem cells, and one triple-negative breast cancer co-culture, made of stromal fibroblasts, adipose derived stem cells, and triple-negative breast cancer cells. After irradiation, growth and decellularization of co-cultures, we reseeded the breast cancer cells for 24 h and analyzed the samples using mass spectrometry. Proteomic analysis revealed that collagen VI, a highly oncogenic collagen isoform linked to breast cancer, was decreased in the irradiated cancer co-culture. This indicates that the anti-cancer impact of radiation may be not only cell ablative, but also influential in creating a less oncogenic microenvironment.
    MeSH term(s) Breast Neoplasms/metabolism ; Carcinogenesis/metabolism ; Cell Line, Tumor ; Coculture Techniques ; Collagen/metabolism ; Extracellular Matrix/metabolism ; Female ; Humans ; Proteomics ; Triple Negative Breast Neoplasms/pathology ; Tumor Microenvironment
    Chemical Substances Collagen (9007-34-5)
    Language English
    Publishing date 2022-07-27
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23158265
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  7. Article ; Online: Nuclear Fragility in Radiation-Induced Senescence: Blebs and Tubes Visualized by 3D Electron Microscopy.

    Freyter, Benjamin M / Abd Al-Razaq, Mutaz A / Isermann, Anna / Dietz, Anne / Azimzadeh, Omid / Hekking, Liesbeth / Gomolka, Maria / Rübe, Claudia E

    Cells

    2022  Volume 11, Issue 2

    Abstract: Irreparable DNA damage following ionizing radiation (IR) triggers prolonged DNA damage response and induces premature senescence. Cellular senescence is a permanent state of cell-cycle arrest characterized by chromatin restructuring, altered nuclear ... ...

    Abstract Irreparable DNA damage following ionizing radiation (IR) triggers prolonged DNA damage response and induces premature senescence. Cellular senescence is a permanent state of cell-cycle arrest characterized by chromatin restructuring, altered nuclear morphology and acquisition of secretory phenotype, which contributes to senescence-related inflammation. However, the mechanistic connections for radiation-induced DNA damage that trigger these senescence-associated hallmarks are poorly understood. In our in vitro model of radiation-induced senescence, mass spectrometry-based proteomics was combined with high-resolution imaging techniques to investigate the interrelations between altered chromatin compaction, nuclear envelope destabilization and nucleo-cytoplasmic chromatin blebbing. Our findings confirm the general pathophysiology of the senescence-response, with disruption of nuclear lamin organization leading to extensive chromatin restructuring and destabilization of the nuclear membrane with release of chromatin fragments into the cytosol, thereby activating cGAS-STING-dependent interferon signaling. By serial block-face scanning electron microscopy (SBF-SEM) whole-cell datasets were acquired to investigate the morphological organization of senescent fibroblasts. High-resolution 3-dimensional (3D) reconstruction of the complex nuclear shape allows us to precisely visualize the segregation of nuclear blebs from the main nucleus and their fusion with lysosomes. By multi-view 3D electron microscopy, we identified nanotubular channels formed in lamin-perturbed nuclei of senescent fibroblasts; the potential role of these nucleo-cytoplasmic nanotubes for expulsion of damaged chromatin has to be examined.
    MeSH term(s) Cell Line ; Cell Nucleus/pathology ; Cell Nucleus/radiation effects ; Cell Nucleus/ultrastructure ; Cell Shape/radiation effects ; Cellular Senescence/radiation effects ; Chromatin Assembly and Disassembly ; Fibroblasts/pathology ; Fibroblasts/radiation effects ; Fibroblasts/ultrastructure ; Humans ; Imaging, Three-Dimensional ; Microscopy, Electron ; Nanotubes/ultrastructure ; Proteomics ; Radiation, Ionizing
    Language English
    Publishing date 2022-01-13
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells11020273
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  8. Article ; Online: Radiation Adverse Outcome pathways (AOPs): examining priority questions from an international horizon-style exercise.

    Chauhan, Vinita / Beaton, Danielle / Tollefsen, Knut Erik / Preston, Julian / Burtt, Julie J / Leblanc, Julie / Hamada, Nobuyuki / Azzam, Edouard I / Armant, Olivier / Bouffler, Simon / Azimzadeh, Omid / Moertl, Simone / Yamada, Yutaka / Tanaka, Ignacia B / Kaiser, Jan Christian / Applegate, Kimberly / Laurier, Dominique / Garnier-Laplace, Jacqueline

    International journal of radiation biology

    2024  , Page(s) 1–14

    Abstract: Purpose: The Organisation for Economic Co-operation and Development (OECD) Adverse Outcome Pathway (AOP) Development Programme is being explored in the radiation field, as an overarching framework to identify and prioritize research needs that best ... ...

    Abstract Purpose: The Organisation for Economic Co-operation and Development (OECD) Adverse Outcome Pathway (AOP) Development Programme is being explored in the radiation field, as an overarching framework to identify and prioritize research needs that best support strengthening of radiation risk assessment and risk management strategies. To advance the use of AOPs, an international horizon-style exercise (HSE) was initiated through the Radiation/Chemical AOP Joint Topical Group (JTG) formed by the OECD Nuclear Energy Agency (NEA) High-Level Group on Low Dose Research (HLG-LDR) under the auspices of the Committee on Radiological Protection and Public Health (CRPPH). The intent of the HSE was to identify key research questions for consideration in AOP development that would help to reduce uncertainties in estimating the health risks following exposures to low dose and low dose-rate ionizing radiation. The HSE was conducted in several phases involving the solicitation of relevant questions, a collaborative review of open-ended candidate questions and an elimination exercise that led to the selection of 25 highest priority questions for the stated purpose. These questions were further ranked by over 100 respondents through an international survey. This final set of questions was judged to provide insights into how the OECD's AOP approach can be put into practice to meet the needs of hazard and risk assessors, regulators, and researchers. This paper examines the 25 priority questions in the context of hazard/risk assessment framework for ionizing radiation.
    Conclusion: By addressing the 25 priority questions, it is anticipated that constructed AOPs will have a high level of specificity, making them valuable tools for simplifying and prioritizing complex biological processes for use in developing revised radiation hazard and risk assessment strategies.
    Language English
    Publishing date 2024-05-08
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 3065-x
    ISSN 1362-3095 ; 0020-7616 ; 0955-3002
    ISSN (online) 1362-3095
    ISSN 0020-7616 ; 0955-3002
    DOI 10.1080/09553002.2024.2348072
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  9. Article: Late Effects of Chronic Low Dose Rate Total Body Irradiation on the Heart Proteome of ApoE

    Azimzadeh, Omid / Merl-Pham, Juliane / Subramanian, Vikram / Oleksenko, Kateryna / Krumm, Franziska / Mancuso, Mariateresa / Pasquali, Emanuela / Tanaka, Ignacia B / Tanaka, Satoshi / Atkinson, Michael J / Tapio, Soile / Moertl, Simone

    Cancers

    2023  Volume 15, Issue 13

    Abstract: Recent epidemiologic studies support an association between chronic low-dose radiation exposure and the development of cardiovascular disease (CVD). The molecular mechanisms underlying the adverse effect of chronic low dose exposure are not fully ... ...

    Abstract Recent epidemiologic studies support an association between chronic low-dose radiation exposure and the development of cardiovascular disease (CVD). The molecular mechanisms underlying the adverse effect of chronic low dose exposure are not fully understood. To address this issue, we have investigated changes in the heart proteome of ApoE deficient (ApoE
    Language English
    Publishing date 2023-06-29
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15133417
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  10. Article ; Online: Data-Independent Acquisition Proteomics Reveals Long-Term Biomarkers in the Serum of C57BL/6J Mice Following Local High-Dose Heart Irradiation.

    Azimzadeh, Omid / von Toerne, Christine / Subramanian, Vikram / Sievert, Wolfgang / Multhoff, Gabriele / Atkinson, Michael J / Tapio, Soile

    Frontiers in public health

    2021  Volume 9, Page(s) 678856

    Abstract: Background and Purpose: ...

    Abstract Background and Purpose:
    MeSH term(s) Animals ; Biomarkers/blood ; Heart/radiation effects ; Mice ; Mice, Inbred C57BL ; Proteome ; Proteomics
    Chemical Substances Biomarkers ; Proteome
    Language English
    Publishing date 2021-07-02
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2711781-9
    ISSN 2296-2565 ; 2296-2565
    ISSN (online) 2296-2565
    ISSN 2296-2565
    DOI 10.3389/fpubh.2021.678856
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