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Challenges of Radiation Biology for Cancer Management 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 6845

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Guest Editor
Faculty of Medicine, Biophysics Institute, University of Coimbra, Coimbra, Portugal
Interests: biophysics; oncobiology; radiobiology; preclinical models; new therapeutics
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Faculty of Medicine, Biophysics Institute, University of Coimbra, Coimbra, Portugal
Interests: brain–computer interfaces; artificial intelligence; biomaterials
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Radiobiology explores the biological effects of radiation and represents a fundamental scientific area regarding the management of cancer, which is expected to attain maximum impact in the treatment of individual cancer patients. Any insights in radiation biology contribute to innovation and progress in the field of radiation oncology. The continuous improvements of research models and technologies broaden the potential for major advances in radiation research and create new challenges. This Special Issue on “Challenges of Radiation Biology for Cancer Management 2.0” encompasses all aspects of radiobiology that could expand the current understanding on cellular and molecular mechanisms of tumor and normal tissue responses to ionizing radiation, induced radiation resistance, radiation therapy sensitization, biomarkers of radiation response, radiation and immunotherapy combined approaches, and targeted radiation therapy. Works reporting new insights on the biological effects of radiation related to tumor metabolism, cancer stem cells, tumor microenvironment, and new anti-cancer therapeutic approaches are particularly encouraged. This Special Issue will include original articles as well as reviews on these topics.

Dr. Salomé Pires
Prof. Dr. Maria Filomena Botelho
Guest Editors

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Keywords

  • radiobiology
  • cancer
  • molecular mechanisms
  • radiosensitizers
  • radio-resistance
  • radiotherapy
  • targeted radiation therapy
  • biomarkers
  • tumor microenvironment
  • radio-immunotherapy

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Published Papers (3 papers)

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Research

19 pages, 6747 KiB  
Article
In Vivo Radiobiological Investigations with the TOP-IMPLART Proton Beam on a Medulloblastoma Mouse Model
by Daniela Giovannini, Cinzia De Angelis, Maria Denise Astorino, Emiliano Fratini, Evaristo Cisbani, Giulia Bazzano, Alessandro Ampollini, Massimo Piccinini, Enrico Nichelatti, Emiliano Trinca, Paolo Nenzi, Mariateresa Mancuso, Luigi Picardi, Carmela Marino, Concetta Ronsivalle and Simonetta Pazzaglia
Int. J. Mol. Sci. 2023, 24(9), 8281; https://doi.org/10.3390/ijms24098281 - 5 May 2023
Cited by 2 | Viewed by 1745
Abstract
Protons are now increasingly used to treat pediatric medulloblastoma (MB) patients. We designed and characterized a setup to deliver proton beams for in vivo radiobiology experiments at a TOP-IMPLART facility, a prototype of a proton-therapy linear accelerator developed at the ENEA Frascati Research [...] Read more.
Protons are now increasingly used to treat pediatric medulloblastoma (MB) patients. We designed and characterized a setup to deliver proton beams for in vivo radiobiology experiments at a TOP-IMPLART facility, a prototype of a proton-therapy linear accelerator developed at the ENEA Frascati Research Center, with the goal of assessing the feasibility of TOP-IMPLART for small animal proton therapy research. Mice bearing Sonic-Hedgehog (Shh)-dependent MB in the flank were irradiated with protons to test whether irradiation could be restricted to a specific depth in the tumor tissue and to compare apoptosis induced by the same dose of protons or photons. In addition, the brains of neonatal mice at postnatal day 5 (P5), representing a very small target, were irradiated with 6 Gy of protons with two different collimated Spread-Out Bragg Peaks (SOBPs). Apoptosis was visualized by immunohistochemistry for the apoptotic marker caspase-3-activated, and quantified by Western blot. Our findings proved that protons could be delivered to the upper part while sparing the deepest part of MB. In addition, a comparison of the effectiveness of protons and photons revealed a very similar increase in the expression of cleaved caspase-3. Finally, by using a very small target, the brain of P5-neonatal mice, we demonstrated that the proton irradiation field reached the desired depth in brain tissue. Using the TOP-IMPLART accelerator we established setup and procedures for proton irradiation, suitable for translational preclinical studies. This is the first example of in vivo experiments performed with a “full-linac” proton-therapy accelerator. Full article
(This article belongs to the Special Issue Challenges of Radiation Biology for Cancer Management 2.0)
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14 pages, 3740 KiB  
Article
Mitochondrial Metabolism in X-Irradiated Cells Undergoing Irreversible Cell-Cycle Arrest
by Eri Hirose, Miho Noguchi, Tomokazu Ihara and Akinari Yokoya
Int. J. Mol. Sci. 2023, 24(3), 1833; https://doi.org/10.3390/ijms24031833 - 17 Jan 2023
Cited by 5 | Viewed by 2109
Abstract
Irreversible cell-cycle-arrested cells not undergoing cell divisions have been thought to be metabolically less active because of the unnecessary consumption of energy for cell division. On the other hand, they might be actively involved in the tissue microenvironment through an inflammatory response. In [...] Read more.
Irreversible cell-cycle-arrested cells not undergoing cell divisions have been thought to be metabolically less active because of the unnecessary consumption of energy for cell division. On the other hand, they might be actively involved in the tissue microenvironment through an inflammatory response. In this study, we examined the mitochondria-dependent metabolism in human cells irreversibly arrested in response to ionizing radiation to confirm this possibility. Human primary WI-38 fibroblast cells and the BJ-5ta fibroblast-like cell line were exposed to 20 Gy X-rays and cultured for up to 9 days after irradiation. The mitochondrial morphology and membrane potential were evaluated in the cells using the mitochondrial-specific fluorescent reagents MitoTracker Green (MTG) and 5,5′,6,6′-tetraethyl-benzimidazolylcarbocyanine iodide (JC-1), respectively. The ratio of the mean MTG-stained total mitochondrial area per unit cell area decreased for up to 9 days after X-irradiation. The fraction of the high mitochondrial membrane potential area visualized by JC-1 staining reached its minimum 2 days after irradiation and then increased (particularly, WI-38 cells increased 1.8-fold the value of the control). Their chronological changes indicate that the mitochondrial volume in the irreversible cell-cycle-arrested cells showed significant increase concurrently with cellular volume expansion, indicating that the mitochondria-dependent energy metabolism was still active. These results indicate that the energy metabolism in X-ray-induced senescent-like cells is active compared to nonirradiated normal cells, even though they do not undergo cell divisions. Full article
(This article belongs to the Special Issue Challenges of Radiation Biology for Cancer Management 2.0)
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21 pages, 2871 KiB  
Article
Effectiveness of Flattening-Filter-Free versus Flattened Beams in V79 and Glioblastoma Patient-Derived Stem-like Cells
by Valentina Dini, Giuseppe Esposito, Andrea Sacconi, Marco D’Andrea, Maria Antonella Tabocchini, Pasquale Anello, Lucia Ricci-Vitiani, Mariachiara Buccarelli, Roberto Pallini and Lidia Strigari
Int. J. Mol. Sci. 2023, 24(2), 1107; https://doi.org/10.3390/ijms24021107 - 6 Jan 2023
Cited by 2 | Viewed by 2280
Abstract
Literature data on the administration of conventional high-dose beams with (FF) or without flattening filters (FFF) show conflicting results on biological effects at the cellular level. To contribute to this field, we irradiated V79 Chinese hamster lung fibroblasts and two patient-derived glioblastoma stem-like [...] Read more.
Literature data on the administration of conventional high-dose beams with (FF) or without flattening filters (FFF) show conflicting results on biological effects at the cellular level. To contribute to this field, we irradiated V79 Chinese hamster lung fibroblasts and two patient-derived glioblastoma stem-like cell lines (GSCs—named #1 and #83) using a clinical 10 MV accelerator with FF (at 4 Gy/min) and FFF (at two dose rates 4 and 24 Gy/min). Cell killing and DNA damage induction, determined using the γ-H2AX assay, and gene expression were studied. No significant differences in the early survival of V79 cells were observed as a function of dose rates and FF or FFF beams, while a trend of reduction in late survival was observed at the highest dose rate with the FFF beam. GSCs showed similar survival levels as a function of dose rates, both delivered in the FFF regimen. The amount of DNA damage measured for both dose rates after 2 h was much higher in line #1 than in line #83, with statistically significant differences between the two dose rates only in line #83. The gene expression analysis of the two GSC lines indicates gene signatures mimicking the prognosis of glioblastoma (GBM) patients derived from a public database. Overall, the results support the current use of FFF and highlight the possibility of identifying patients with candidate gene signatures that could benefit from irradiation with FFF beams at a high dose rate. Full article
(This article belongs to the Special Issue Challenges of Radiation Biology for Cancer Management 2.0)
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