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  1. Article: Gene Therapy for Systemic or Organ Specific Delivery of Manganese Superoxide Dismutase.

    Greenberger, Joel S / Mukherjee, Amitava / Epperly, Michael W

    Antioxidants (Basel, Switzerland)

    2021  Volume 10, Issue 7

    Abstract: ... as a radioprotector, several prominent observations were made by Larry Oberley, Joel Greenberger, and Michael Epperly ...

    Abstract Manganese superoxide dismutase (MnSOD) is a dominant component of the antioxidant defense system in mammalian cells. Since ionizing irradiation induces profound oxidative stress, it was logical to test the effect of overexpression of MnSOD on radioresistance. This task was accomplished by introduction of a transgene for MnSOD into cells in vitro and into organs in vivo, and both paradigms showed clear radioresistance following overexpression. During the course of development and clinical application of using MnSOD as a radioprotector, several prominent observations were made by Larry Oberley, Joel Greenberger, and Michael Epperly which include (1) mitochondrial localization of either manganese superoxide dismutase or copper/zinc SOD was required to provide optimal radiation protection; (2) the time required for optimal expression was 12-18 h, and while acceptable for radiation protection, the time delay was impractical for radiation mitigation; (3) significant increases in intracellular elevation of MnSOD activity were required for effective radioprotection. Lessons learned during the development of MnSOD gene therapy have provided a strategy for delivery of small molecule SOD mimics, which are faster acting and have shown the potential for both radiation protection and mitigation. The purpose of this review is to summarize the current status of using MnSOD-PL and SOD mimetics as radioprotectors and radiomitigators.
    Language English
    Publishing date 2021-06-30
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox10071057
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  2. Article: Gene Therapy for Systemic or Organ Specific Delivery of Manganese Superoxide Dismutase

    Greenberger, Joel S. / Mukherjee, Amitava / Epperly, Michael W.

    Antioxidants. 2021 June 30, v. 10, no. 7

    2021  

    Abstract: ... as a radioprotector, several prominent observations were made by Larry Oberley, Joel Greenberger, and Michael Epperly ...

    Abstract Manganese superoxide dismutase (MnSOD) is a dominant component of the antioxidant defense system in mammalian cells. Since ionizing irradiation induces profound oxidative stress, it was logical to test the effect of overexpression of MnSOD on radioresistance. This task was accomplished by introduction of a transgene for MnSOD into cells in vitro and into organs in vivo, and both paradigms showed clear radioresistance following overexpression. During the course of development and clinical application of using MnSOD as a radioprotector, several prominent observations were made by Larry Oberley, Joel Greenberger, and Michael Epperly which include (1) mitochondrial localization of either manganese superoxide dismutase or copper/zinc SOD was required to provide optimal radiation protection; (2) the time required for optimal expression was 12–18 h, and while acceptable for radiation protection, the time delay was impractical for radiation mitigation; (3) significant increases in intracellular elevation of MnSOD activity were required for effective radioprotection. Lessons learned during the development of MnSOD gene therapy have provided a strategy for delivery of small molecule SOD mimics, which are faster acting and have shown the potential for both radiation protection and mitigation. The purpose of this review is to summarize the current status of using MnSOD-PL and SOD mimetics as radioprotectors and radiomitigators.
    Keywords antioxidant activity ; copper ; gene therapy ; irradiation ; mammals ; mitochondria ; oxidative stress ; radiation resistance ; radioprotective agents ; radioprotective effect ; superoxide dismutase ; transgenes ; zinc
    Language English
    Dates of publication 2021-0630
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox10071057
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: RE: Valstar et al., "The tubarial salivary glands: A potential new organ at risk for radiotherapy".

    Ellsworth, Susannah G / Winkfield, Karen M / Greenberger, Joel S

    Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

    2020  Volume 154, Page(s) 312–313

    MeSH term(s) Humans ; Radiation Oncology ; Radiotherapy Dosage ; Salivary Glands
    Language English
    Publishing date 2020-12-11
    Publishing country Ireland
    Document type Letter ; Comment
    ZDB-ID 605646-5
    ISSN 1879-0887 ; 0167-8140
    ISSN (online) 1879-0887
    ISSN 0167-8140
    DOI 10.1016/j.radonc.2020.12.002
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    Zs.A 1926: Show issues Location:
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  4. Article ; Online: Metformin and adipose-derived stem cell combination therapy alleviates radiation-induced skin fibrosis in mice.

    Malekzadeh, Hamid / Surucu, Yusuf / Chinnapaka, Somaiah / Yang, Katherine S / Arellano, José A / Samadi, Yasamin / Epperly, Michael W / Greenberger, Joel S / Rubin, J Peter / Ejaz, Asim

    Stem cell research & therapy

    2024  Volume 15, Issue 1, Page(s) 13

    Abstract: Background: Radiation therapy often leads to late radiation-induced skin fibrosis (RISF), causing movement impairment and discomfort. We conducted a comprehensive study to assess the effectiveness of metformin and adipose-derived stem cells (ASCs), ... ...

    Abstract Background: Radiation therapy often leads to late radiation-induced skin fibrosis (RISF), causing movement impairment and discomfort. We conducted a comprehensive study to assess the effectiveness of metformin and adipose-derived stem cells (ASCs), whether autologous or allogeneic, individually or in combination therapy, in mitigating RISF.
    Methods: Using a female C57BL/6J mouse model subjected to hind limb irradiation as a representative RISF model, we evaluated metformin, ASCs, or their combination in two contexts: prophylactic (started on day 1 post-irradiation) and therapeutic (initiated on day 14 post-irradiation, coinciding with fibrosis symptoms). We measured limb movement, examined skin histology, and analyzed gene expression to assess treatment efficacy.
    Results: Prophylactic metformin and ASCs, whether autologous or allogeneic, effectively prevented late fibrosis, with metformin showing promising results. However, combination therapy did not provide additional benefits when used prophylactically. Autologous ASCs, alone or with metformin, proved most effective against late-stage RISF. Prophylactic intervention outperformed late therapy for mitigating radiation skin damage. Co-culture studies revealed that ASCs and metformin downregulated inflammation and fibrotic gene expression in both mouse and human fibroblasts.
    Conclusions: Our study suggests metformin's potential as a prophylactic measure to prevent RISF, and the combination of ASCs and metformin holds promise for late-stage RISF treatment. These findings have clinical implications for improving the quality of life for those affected by radiation-induced skin fibrosis.
    MeSH term(s) Humans ; Female ; Animals ; Mice ; Mice, Inbred C57BL ; Quality of Life ; Metformin/pharmacology ; Metformin/therapeutic use ; Fibrosis ; Stem Cells
    Chemical Substances Metformin (9100L32L2N)
    Language English
    Publishing date 2024-01-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 2548671-8
    ISSN 1757-6512 ; 1757-6512
    ISSN (online) 1757-6512
    ISSN 1757-6512
    DOI 10.1186/s13287-023-03627-7
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  5. Article: Use of a Therapeutic Trial of Graduated Neoadjuvant Radiation Therapy for Locally Advanced Esophageal Cancer in a Patient With Fanconi Anemia.

    Gardner, Ulysses G / Wood, Stephanie G / Chen, Emerson Y / Greenberger, Joel S / Grossberg, Aaron J

    Advances in radiation oncology

    2021  Volume 7, Issue 1, Page(s) 100810

    Language English
    Publishing date 2021-09-29
    Publishing country United States
    Document type Case Reports
    ISSN 2452-1094
    ISSN 2452-1094
    DOI 10.1016/j.adro.2021.100810
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  6. Article ; Online: Carcinogen 4-Nitroquinoline Oxide (4-NQO) Induces Oncostatin-M (OSM) in Esophageal Cells.

    Mukherjee, Amitava / Epperly, Michael W / Fisher, Renee / Shields, Donna / Hou, Wen / Pennathur, Arjun / Luketich, James / Wang, Hong / Greenberger, Joel S

    In vivo (Athens, Greece)

    2023  Volume 37, Issue 2, Page(s) 506–518

    Abstract: Background/aim: The earliest cellular and molecular biologic changes in the esophagus that lead to esophageal cancer were evaluated in a mouse model. We correlated numbers of senescent cells with the levels of expression of potentially carcinogenic ... ...

    Abstract Background/aim: The earliest cellular and molecular biologic changes in the esophagus that lead to esophageal cancer were evaluated in a mouse model. We correlated numbers of senescent cells with the levels of expression of potentially carcinogenic genes in sorted side population (SP) cells containing esophageal stem cells and non-stem cells in the non-side population cells in the 4-nitroquinolone oxide (NQO)-treated esophagus.
    Materials and methods: We compared stem cells with non-stem cells from the esophagus of mice treated with the chemical carcinogen 4-NQO (100 μg/ml) in drinking water. We also compared gene expression in human esophagus samples treated with 4-NQO (100 μg/ml media) to non-treated samples. We separated and quantitated the relative levels of expression of RNA using RNAseq analysis. We identified senescent cells by luciferase imaging of p16
    Results: A significant increase in the levels of RNA for oncostatin-M was found in senescent cells of the esophagus from 4-NQO-treated mice and human esophagus in vitro.
    Conclusion: Induction of OSM in chemically-induced esophageal cancer in mice correlates with the appearance of senescent cells.
    MeSH term(s) Humans ; Animals ; Mice ; Carcinogens ; Oxides ; Mutagens ; Esophageal Neoplasms/chemically induced ; Esophageal Neoplasms/genetics ; Nitroquinolines ; RNA ; Oncostatin M
    Chemical Substances Carcinogens ; Oxides ; Mutagens ; Nitroquinolines ; RNA (63231-63-0) ; OSM protein, human ; Oncostatin M (106956-32-5)
    Language English
    Publishing date 2023-03-07
    Publishing country Greece
    Document type Journal Article
    ZDB-ID 807031-3
    ISSN 1791-7549 ; 0258-851X
    ISSN (online) 1791-7549
    ISSN 0258-851X
    DOI 10.21873/invivo.13108
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    Zs.A 2288: Show issues Location:
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  7. Article: Genetically Engineered Probiotic

    Hamade, Diala F / Epperly, Michael W / Fisher, Renee / Hou, Wen / Shields, Donna / van Pijkeren, Jan-Peter / Leibowitz, Brian J / Coffman, Lan G / Wang, Hong / Huq, M Saiful / Huang, Ziyu / Rogers, Claude J / Vlad, Anda M / Greenberger, Joel S / Mukherjee, Amitava

    Cancers

    2024  Volume 16, Issue 3

    Abstract: Despite recent advances in cancer therapy, ovarian cancer remains the most lethal gynecological cancer worldwide, making it crucial and of the utmost importance to establish novel therapeutic strategies. Adjuvant radiotherapy has been assessed ... ...

    Abstract Despite recent advances in cancer therapy, ovarian cancer remains the most lethal gynecological cancer worldwide, making it crucial and of the utmost importance to establish novel therapeutic strategies. Adjuvant radiotherapy has been assessed historically, but its use was limited by intestinal toxicity. We recently established the role of
    Language English
    Publishing date 2024-01-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers16030474
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  8. Article ; Online: Understanding the mechanism of radiation induced fibrosis and therapy options.

    Ejaz, Asim / Greenberger, Joel S / Rubin, Peter J

    Pharmacology & therapeutics

    2019  Volume 204, Page(s) 107399

    Abstract: Radiation therapy has been increasingly employed as a tool to cure and palliate majority of solid tumors. Although radiotherapy has shown promising results in preserving structure and function of organs, it is associated with late side effects mainly ... ...

    Abstract Radiation therapy has been increasingly employed as a tool to cure and palliate majority of solid tumors. Although radiotherapy has shown promising results in preserving structure and function of organs, it is associated with late side effects mainly manifested in the form of tissue fibrosis. Recent advances in molecular biology techniques has helped better understand the molecular mechanisms involved in radiation induced fibrosis. Currently, very few treatment modalities are available to treat the condition with moderate success rate. Stem cell therapies and particularly adipose tissue and adipose derived stem cells therapies have shown promising results in clinical applications. Identification of the key factors involved in the mitigation process will help to enhance the beneficial effects and develop new therapy approaches.
    MeSH term(s) Animals ; Fibrosis/therapy ; Humans ; Radiotherapy/adverse effects ; Stem Cell Transplantation/methods
    Language English
    Publishing date 2019-08-13
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 194735-7
    ISSN 1879-016X ; 0163-7258
    ISSN (online) 1879-016X
    ISSN 0163-7258
    DOI 10.1016/j.pharmthera.2019.107399
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    Zs.A 1183: Show issues Location:
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  9. Article ; Online: Metformin and adipose-derived stem cell combination therapy alleviates radiation-induced skin fibrosis in mice

    Hamid Malekzadeh / Yusuf Surucu / Somaiah Chinnapaka / Katherine S. Yang / José A. Arellano / Yasamin Samadi / Michael W. Epperly / Joel S. Greenberger / J. Peter Rubin / Asim Ejaz

    Stem Cell Research & Therapy, Vol 15, Iss 1, Pp 1-

    2024  Volume 17

    Abstract: Abstract Background Radiation therapy often leads to late radiation-induced skin fibrosis (RISF), causing movement impairment and discomfort. We conducted a comprehensive study to assess the effectiveness of metformin and adipose-derived stem cells (ASCs) ...

    Abstract Abstract Background Radiation therapy often leads to late radiation-induced skin fibrosis (RISF), causing movement impairment and discomfort. We conducted a comprehensive study to assess the effectiveness of metformin and adipose-derived stem cells (ASCs), whether autologous or allogeneic, individually or in combination therapy, in mitigating RISF. Methods Using a female C57BL/6J mouse model subjected to hind limb irradiation as a representative RISF model, we evaluated metformin, ASCs, or their combination in two contexts: prophylactic (started on day 1 post-irradiation) and therapeutic (initiated on day 14 post-irradiation, coinciding with fibrosis symptoms). We measured limb movement, examined skin histology, and analyzed gene expression to assess treatment efficacy. Results Prophylactic metformin and ASCs, whether autologous or allogeneic, effectively prevented late fibrosis, with metformin showing promising results. However, combination therapy did not provide additional benefits when used prophylactically. Autologous ASCs, alone or with metformin, proved most effective against late-stage RISF. Prophylactic intervention outperformed late therapy for mitigating radiation skin damage. Co-culture studies revealed that ASCs and metformin downregulated inflammation and fibrotic gene expression in both mouse and human fibroblasts. Conclusions Our study suggests metformin's potential as a prophylactic measure to prevent RISF, and the combination of ASCs and metformin holds promise for late-stage RISF treatment. These findings have clinical implications for improving the quality of life for those affected by radiation-induced skin fibrosis.
    Keywords Radiation ; Fibrosis ; Metformin ; Prophylactic therapy ; Adipose stem cells ; Medicine (General) ; R5-920 ; Biochemistry ; QD415-436
    Subject code 616
    Language English
    Publishing date 2024-01-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Combined injury: irradiation with skin or bone wounds in rodent models.

    Glowacki, Julie / Epperly, Michael W / Bellare, Anuj / Wipf, Peter / Greenberger, Joel S

    Journal of radiological protection : official journal of the Society for Radiological Protection

    2021  Volume 41, Issue 4

    Abstract: ... wound healing was mitigated to different extents by single doses of gramicidin S-nitroxide JP4-039, a plasmid ...

    Abstract A radiation combined injury is defined as an injury that occurs in the setting of irradiation, such as those expected after a nuclear accident, radiation dispersal device release (a 'dirty bomb'), or a nuclear weapon detonation. There is much research on irradiation-associated burns and their healing, but there is less known about other injuries sustained in the context of irradiation. Animal models are limited in their correlations to clinical situations but can support research on specific questions about injuries and their healing. Mouse models of irradiation with skin or bone wounds are validated as highly reproducible and quantitative. They show dose-dependent impairment of wound healing, with later recovery. Irradiation-induced delay of bone wound healing was mitigated to different extents by single doses of gramicidin S-nitroxide JP4-039, a plasmid expressing manganese superoxide dismutase, amifostine/WR2721, or the bifunctional sulfoxide MMS-350. These models should be useful for research on mechanisms of radiation dermal and osseous damage and for further development of new radioprotectors. They also provide information of potential relevance to the effects of clinical radiation therapies.
    MeSH term(s) Animals ; Disease Models, Animal ; Mice ; Radiation Injuries ; Rodentia ; Skin ; Wound Healing
    Language English
    Publishing date 2021-11-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 639411-5
    ISSN 1361-6498 ; 0952-4746
    ISSN (online) 1361-6498
    ISSN 0952-4746
    DOI 10.1088/1361-6498/ac125b
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