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  1. Article: Phytoradiotherapy to enhance cancer treatment outcomes with cannabidiol, bitter melon juice, and plant hemoglobin.

    Alfonzetti, Tyler / Moreau, Michele / Yasmin-Karim, Sayeda / Ngwa, Wilfred / Avery, Stephen / Goia, Denisa

    Frontiers in oncology

    2023  Volume 12, Page(s) 1085686

    Abstract: Despite technological advances in radiation therapy for cancer treatment, many patient populations still experience mediocre survival percentages, local control, and quality of life. Additionally, much of the world lacks access to expensive, modern ... ...

    Abstract Despite technological advances in radiation therapy for cancer treatment, many patient populations still experience mediocre survival percentages, local control, and quality of life. Additionally, much of the world lacks access to expensive, modern treatment options. The need for innovative, cost-effective solutions that can improve patient treatment outcomes is essential. Phytomedicines have been shown to induce apoptotic tumor cell death, diminish tumor progression, reduce cancer incidence, alleviate harmful hypoxic conditions, and more. While an ample amount of research is available that characterizes many phytomedicines as having anti-cancer properties that increase tumor cell killing/control and mitigate the harmful side effects of radiation damage, little work has been done to investigate the synergistic effect of phytoradiotherapy: combining radiation treatment with phytomedicines. In this study, a protocol for testing the radiosensitizing effects of phytomedicines was validated and used to investigate the well-known plant based medicine cannabidiol (CBD) and the lesser-known medicinal fruit Bitter Melon. Additionally, based on its high concentration of plant hemoglobin which has been shown to abate hypoxia, the African-indigenous
    Language English
    Publishing date 2023-01-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.1085686
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Comparison of FLASH Proton Entrance and the Spread-Out Bragg Peak Dose Regions in the Sparing of Mouse Intestinal Crypts and in a Pancreatic Tumor Model.

    Kim, Michele M / Verginadis, Ioannis I / Goia, Denisa / Haertter, Allison / Shoniyozov, Khayrullo / Zou, Wei / Maity, Amit / Busch, Theresa M / Metz, James M / Cengel, Keith A / Dong, Lei / Koumenis, Costas / Diffenderfer, Eric S

    Cancers

    2021  Volume 13, Issue 16

    Abstract: Ultra-high dose rate FLASH proton radiotherapy (F-PRT) has been shown to reduce normal tissue toxicity compared to standard dose rate proton radiotherapy (S-PRT) in experiments using the entrance portion of the proton depth dose profile, while proton ... ...

    Abstract Ultra-high dose rate FLASH proton radiotherapy (F-PRT) has been shown to reduce normal tissue toxicity compared to standard dose rate proton radiotherapy (S-PRT) in experiments using the entrance portion of the proton depth dose profile, while proton therapy uses a spread-out Bragg peak (SOBP) with unknown effects on FLASH toxicity sparing. To investigate, the biological effects of F-PRT using an SOBP and the entrance region were compared to S-PRT in mouse intestine. In this study, 8-10-week-old C57BL/6J mice underwent 15 Gy (absorbed dose) whole abdomen irradiation in four groups: (1) SOBP F-PRT, (2) SOBP S-PRT, (3) entrance F-PRT, and (4) entrance S-PRT. Mice were injected with EdU 3.5 days after irradiation, and jejunum segments were harvested and preserved. EdU-positive proliferating cells and regenerated intestinal crypts were quantified. The SOBP had a modulation (width) of 2.5 cm from the proximal to distal 90%. Dose rates with a SOBP for F-PRT or S-PRT were 108.2 ± 8.3 Gy/s or 0.82 ± 0.14 Gy/s, respectively. In the entrance region, dose rates were 107.1 ± 15.2 Gy/s and 0.83 ± 0.19 Gy/s, respectively. Both entrance and SOBP F-PRT preserved a significantly higher number of EdU + /crypt cells and percentage of regenerated crypts compared to S-PRT. Moreover, tumor growth studies showed no difference between SOBP and entrance for either of the treatment modalities.
    Language English
    Publishing date 2021-08-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13164244
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A Novel Mouse Model of Radiation-Induced Cardiac Injury Reveals Biological and Radiological Biomarkers of Cardiac Dysfunction with Potential Clinical Relevance.

    Dreyfuss, Alexandra D / Goia, Denisa / Shoniyozov, Khayrullo / Shewale, Swapnil V / Velalopoulou, Anastasia / Mazzoni, Susan / Avgousti, Harris / Metzler, Scott D / Bravo, Paco E / Feigenberg, Steven J / Ky, Bonnie / Verginadis, Ioannis I / Koumenis, Constantinos

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2021  Volume 27, Issue 8, Page(s) 2266–2276

    Abstract: Purpose: Radiation-induced cardiotoxicity is a significant concern in thoracic oncology patients. However, the basis for this disease pathology is not well characterized. We developed a novel mouse model of radiation-induced cardiotoxicity to ... ...

    Abstract Purpose: Radiation-induced cardiotoxicity is a significant concern in thoracic oncology patients. However, the basis for this disease pathology is not well characterized. We developed a novel mouse model of radiation-induced cardiotoxicity to investigate pathophysiologic mechanisms and identify clinically targetable biomarkers of cardiac injury.
    Experimental design: Single radiation doses of 20, 40, or 60 Gy were delivered to the cardiac apex of female C57BL/6 mice ages 9-11 weeks, with or without adjacent lung tissue, using conformal radiotherapy. Cardiac tissue was harvested up to 24 weeks post-radiotherapy for histologic analysis. Echocardiography and Technetium-99m sestamibi single photon emission computed tomography (SPECT) at 8 and 16 weeks post-radiotherapy were implemented to evaluate myocardial function and perfusion. Mouse cardiac tissue and mouse and human plasma were harvested for biochemical studies.
    Results: Histopathologically, radiotherapy resulted in perivascular fibrosis 8 and 24 (
    Conclusions: We developed and characterized a pathophysiologically relevant mouse model of radiation-induced cardiotoxicity involving
    MeSH term(s) Animals ; Biomarkers/analysis ; Cardiotoxicity/diagnosis ; Cardiotoxicity/etiology ; Cardiotoxicity/pathology ; Dose-Response Relationship, Radiation ; Echocardiography ; Female ; Fibrosis ; Heart/diagnostic imaging ; Heart/radiation effects ; Humans ; Lung Neoplasms/radiotherapy ; Mice ; Myocardium/pathology ; Radiation Injuries, Experimental/diagnosis ; Radiation Injuries, Experimental/etiology ; Radiation Injuries, Experimental/pathology ; Tomography, Emission-Computed, Single-Photon
    Chemical Substances Biomarkers
    Language English
    Publishing date 2021-02-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-20-3882
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4223: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Design, Implementation, and in Vivo Validation of a Novel Proton FLASH Radiation Therapy System.

    Diffenderfer, Eric S / Verginadis, Ioannis I / Kim, Michele M / Shoniyozov, Khayrullo / Velalopoulou, Anastasia / Goia, Denisa / Putt, Mary / Hagan, Sarah / Avery, Stephen / Teo, Kevin / Zou, Wei / Lin, Alexander / Swisher-McClure, Samuel / Koch, Cameron / Kennedy, Ann R / Minn, Andy / Maity, Amit / Busch, Theresa M / Dong, Lei /
    Koumenis, Costas / Metz, James / Cengel, Keith A

    International journal of radiation oncology, biology, physics

    2020  Volume 106, Issue 2, Page(s) 440–448

    Abstract: Purpose: Recent studies suggest that ultrahigh-dose-rate, "FLASH," electron radiation therapy (RT) decreases normal tissue damage while maintaining tumor response compared with conventional dose rate RT. Here, we describe a novel RT apparatus that ... ...

    Abstract Purpose: Recent studies suggest that ultrahigh-dose-rate, "FLASH," electron radiation therapy (RT) decreases normal tissue damage while maintaining tumor response compared with conventional dose rate RT. Here, we describe a novel RT apparatus that delivers FLASH proton RT (PRT) using double scattered protons with computed tomography guidance and provide the first report of proton FLASH RT-mediated normal tissue radioprotection.
    Methods and materials: Absolute dose was measured at multiple depths in solid water and validated against an absolute integral charge measurement using a Faraday cup. Real-time dose rate was obtained using a NaI detector to measure prompt gamma rays. The effect of FLASH versus standard dose rate PRT on tumors and normal tissues was measured using pancreatic flank tumors (MH641905) derived from the KPC autochthonous PanCa model in syngeneic C57BL/6J mice with analysis of fibrosis and stem cell repopulation in small intestine after abdominal irradiation.
    Results: The double scattering and collimation apparatus was dosimetrically validated with dose rates of 78 ± 9 Gy per second and 0.9 ± 0.08 Gy per second for the FLASH and standard PRT. Whole abdominal FLASH PRT at 15 Gy significantly reduced the loss of proliferating cells in intestinal crypts compared with standard PRT. Studies with local intestinal irradiation at 18 Gy revealed a reduction to near baseline levels of intestinal fibrosis for FLASH-PRT compared with standard PRT. Despite this difference, FLASH-PRT did not demonstrate tumor radioprotection in MH641905 pancreatic cancer flank tumors after 12 or 18 Gy irradiation.
    Conclusions: We have designed and dosimetrically validated a FLASH-PRT system with accurate control of beam flux on a millisecond time scale and online monitoring of the integral and dose delivery time structure. Using this system, we found that FLASH-PRT decreases acute cell loss and late fibrosis after whole-abdomen and focal intestinal RT, whereas tumor growth inhibition is preserved between the 2 modalities.
    MeSH term(s) Abdomen/radiation effects ; Animals ; Cell Proliferation/radiation effects ; Equipment Design/methods ; Feasibility Studies ; Female ; Fibrosis ; Gamma Rays ; Intestine, Small/pathology ; Intestine, Small/radiation effects ; Mice ; Mice, Inbred C57BL ; Organ Sparing Treatments/instrumentation ; Organ Sparing Treatments/methods ; Organs at Risk/pathology ; Organs at Risk/radiation effects ; Pancreatic Neoplasms/radiotherapy ; Proton Therapy/instrumentation ; Proton Therapy/methods ; Radiation Injuries, Experimental/prevention & control ; Radiation Protection/instrumentation ; Radiation Protection/methods ; Radiometry/methods ; Radiotherapy, Image-Guided/instrumentation ; Radiotherapy, Image-Guided/methods ; Scattering, Radiation ; Stem Cells/radiation effects ; Tomography, X-Ray Computed
    Language English
    Publishing date 2020-01-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Validation Study
    ZDB-ID 197614-x
    ISSN 1879-355X ; 0360-3016
    ISSN (online) 1879-355X
    ISSN 0360-3016
    DOI 10.1016/j.ijrobp.2019.10.049
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1218: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: FLASH Proton Radiotherapy Spares Normal Epithelial and Mesenchymal Tissues While Preserving Sarcoma Response.

    Velalopoulou, Anastasia / Karagounis, Ilias V / Cramer, Gwendolyn M / Kim, Michele M / Skoufos, Giorgos / Goia, Denisa / Hagan, Sarah / Verginadis, Ioannis I / Shoniyozov, Khayrullo / Chiango, June / Cerullo, Michelle / Varner, Kelley / Yao, Lutian / Qin, Ling / Hatzigeorgiou, Artemis G / Minn, Andy J / Putt, Mary / Lanza, Matthew / Assenmacher, Charles-Antoine /
    Radaelli, Enrico / Huck, Jennifer / Diffenderfer, Eric / Dong, Lei / Metz, James / Koumenis, Constantinos / Cengel, Keith A / Maity, Amit / Busch, Theresa M

    Cancer research

    2021  Volume 81, Issue 18, Page(s) 4808–4821

    Abstract: In studies of electron and proton radiotherapy, ultrahigh dose rates of FLASH radiotherapy appear to produce fewer toxicities than standard dose rates while maintaining local tumor control. FLASH-proton radiotherapy (F-PRT) brings the spatial advantages ... ...

    Abstract In studies of electron and proton radiotherapy, ultrahigh dose rates of FLASH radiotherapy appear to produce fewer toxicities than standard dose rates while maintaining local tumor control. FLASH-proton radiotherapy (F-PRT) brings the spatial advantages of PRT to FLASH dose rates (>40 Gy/second), making it important to understand if and how F-PRT spares normal tissues while providing antitumor efficacy that is equivalent to standard-proton radiotherapy (S-PRT). Here we studied PRT damage to skin and mesenchymal tissues of muscle and bone and found that F-PRT of the C57BL/6 murine hind leg produced fewer severe toxicities leading to death or requiring euthanasia than S-PRT of the same dose. RNA-seq analyses of murine skin and bone revealed pathways upregulated by S-PRT yet unaltered by F-PRT, such as apoptosis signaling and keratinocyte differentiation in skin, as well as osteoclast differentiation and chondrocyte development in bone. Corroborating these findings, F-PRT reduced skin injury, stem cell depletion, and inflammation, mitigated late effects including lymphedema, and decreased histopathologically detected myofiber atrophy, bone resorption, hair follicle atrophy, and epidermal hyperplasia. F-PRT was equipotent to S-PRT in control of two murine sarcoma models, including at an orthotopic intramuscular site, thereby establishing its relevance to mesenchymal cancers. Finally, S-PRT produced greater increases in TGFβ1 in murine skin and the skin of canines enrolled in a phase I study of F-PRT versus S-PRT. Collectively, these data provide novel insights into F-PRT-mediated tissue sparing and support its ongoing investigation in applications that would benefit from this sparing of skin and mesenchymal tissues. SIGNIFICANCE: These findings will spur investigation of FLASH radiotherapy in sarcoma and additional cancers where mesenchymal tissues are at risk, including head and neck cancer, breast cancer, and pelvic malignancies.
    MeSH term(s) Animals ; Bone and Bones/pathology ; Bone and Bones/radiation effects ; Disease Models, Animal ; Dogs ; Epithelium/radiation effects ; Female ; Gene Expression Profiling ; Humans ; Mice ; Morbidity ; Muscles/pathology ; Muscles/radiation effects ; Organ Sparing Treatments/methods ; Proton Therapy/adverse effects ; Proton Therapy/methods ; Radiation Injuries/diagnosis ; Radiation Injuries/etiology ; Radiotherapy Dosage ; Sarcoma/metabolism ; Sarcoma/pathology ; Sarcoma/radiotherapy ; Skin/radiation effects ; Treatment Outcome
    Language English
    Publishing date 2021-07-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-21-1500
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.135/5: Show issues Location:
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