Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Challenges of Radiation Biology for Cancer Management

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

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

Deadline for manuscript submissions: closed (20 September 2022) | Viewed by 24439

Share This Special Issue

Special Issue Editors

Dr. Salomé Pires

E-Mail Website
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

Prof. Dr. Maria Filomena Botelho

E-Mail Website
Guest Editor

Faculty of Medicine, Biophysics Institute, University of Coimbra, 3004-531 Coimbra, Portugal
Interests: biophysics of ionizing radiation; radiobiology and radiation effects; biomaterials; animal models for human diseases; new cancer therapies
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” 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

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Radiobiology
Cancer
Molecular mechanisms
Radiosensitizers
Radio-resistance
Radiotherapy
Targeted radiation therapy
Biomarkers
Tumor microenvironment
Radio-immunotherapy

Published Papers (10 papers)

Download All Papers

Research

Jump to: Review

19 pages, 3728 KiB

Open AccessArticle

Exploring the Physical and Biological Aspects of BNCT with a Carboranylmethylbenzo[b]acridone Compound in U87 Glioblastoma Cells

by Ana Belchior, Ana Fernandes, Maxime Lamotte, Andreia Filipa Ferreira da Silva, Raquel S. G. R. Seixas, Artur M. S. Silva and Fernanda Marques

Int. J. Mol. Sci. 2022, 23(23), 14929; https://doi.org/10.3390/ijms232314929 - 29 Nov 2022

Cited by 2 | Viewed by 1253

Abstract

Boron neutron capture therapy (BNCT) is a re-emerging technique for selectively killing tumor cells. Briefly, the mechanism can be described as follows: after the uptake of boron into cells, the thermal neutrons trigger the fission of the boron atoms, releasing the α-particles and recoiling lithium particles and high-energy photons that damage the cells. We performed a detailed study of the reactor dosimetry, cellular dose assessment, and radiobiological effects induced by BNCT in glioblastoma (GBM) cells. At maximum reactor power, neutron fluence rates were ϕ₀ = 6.6 × 10⁷ cm⁻² s⁻¹ (thermal) and θ = 2.4 × 10⁴ cm⁻² s⁻¹ with a photon dose rate of 150 mGy·h⁻¹. These values agreed with simulations to within 85% (thermal neutrons), 78% (epithermal neutrons), and 95% (photons), thereby validating the MCNPX model. The GEANT4 simulations, based on a realistic cell model and measured boron concentrations, showed that >95% of the dose in cells was due to the BNC reaction. Carboranylmethylbenzo[b]acridone (CMBA) is among the different proposed boron delivery agents that has shown promising properties due to its lower toxicity and important cellular uptake in U87 glioblastoma cells. In particular, the results obtained for CBMA reinforce radiobiological effects demonstrating that damage is mostly induced by the incorporated boron with negligible contribution from the culture medium and adjacent cells, evidencing extranuclear cell radiosensitivity. Full article

(This article belongs to the Special Issue Challenges of Radiation Biology for Cancer Management)

► Show Figures

Figure 1

13 pages, 1898 KiB

Open AccessArticle

Cultured Human Foreskin as a Model System for Evaluating Ionizing Radiation-Induced Skin Injury

by Yanick Hippchen, Gargi Tewary, Daniela Jung, Zoé Schmal, Stephan Meessen, Jan Palm and Claudia E. Rübe

Int. J. Mol. Sci. 2022, 23(17), 9830; https://doi.org/10.3390/ijms23179830 - 29 Aug 2022

Cited by 4 | Viewed by 1876

Abstract

Purpose: Precise molecular and cellular mechanisms of radiation-induced dermatitis are incompletely understood. Histone variant H2A.J is associated with cellular senescence and modulates senescence-associated secretory phenotype (SASP) after DNA-damaging insults, such as ionizing radiation (IR). Using ex vivo irradiated cultured foreskin, H2A.J was analyzed as a biomarker of radiation-induced senescence, potentially initiating the inflammatory cascade of radiation-induced skin injury. Methods: Human foreskin explants were collected from young donors, irradiated ex vivo with 10 Gy, and cultured in air-liquid interphase for up to 72 h. At different time-points after ex vivo IR exposure, the foreskin epidermis was analyzed for proliferation and senescence markers by immunofluorescence and immunohistochemical staining of sectioned tissue. Secretion of cytokines was measured in supernatants by ELISA. Using our mouse model with fractionated in vivo irradiation, H2A.J expression was analyzed in epidermal stem/progenitor cell populations localized in different regions of murine hair follicles (HF). Results: Non-vascularized foreskin explants preserved their tissue homeostasis up to 72 h (even after IR exposure), but already non-irradiated foreskin epithelium expressed high levels of H2A.J in all epidermal layers and secreted high amounts of cytokines. Unexpectedly, no further increase in H2A.J expression and no obvious upregulation of cytokine secretion was observed in the foreskin epidermis after ex vivo IR. Undifferentiated keratinocytes in murine HF regions, by contrast, revealed low H2A.J expression in non-irradiated skin and significant radiation-induced H2A.J upregulations at different time-points after IR exposure. Based on its staining characteristics, we presume that H2A.J may have previously underestimated the importance of the epigenetic regulation of keratinocyte maturation. Conclusions: Cultured foreskin characterized by highly keratinized epithelium and specific immunological features is not an appropriate model for studying H2A.J-associated tissue reactions during radiation-induced dermatitis. Full article

(This article belongs to the Special Issue Challenges of Radiation Biology for Cancer Management)

► Show Figures

Figure 1

18 pages, 3543 KiB

Open AccessArticle

Tyro3 Targeting as a Radiosensitizing Strategy in Bladder Cancer through Cell Cycle Dysregulation

by Linda Silina, Florent Dufour, Audrey Rapinat, Cécile Reyes, David Gentien, Fatlinda Maksut, François Radvanyi, Pierre Verrelle, Isabelle Bernard-Pierrot and Frédérique Mégnin-Chanet

Int. J. Mol. Sci. 2022, 23(15), 8671; https://doi.org/10.3390/ijms23158671 - 04 Aug 2022

Cited by 3 | Viewed by 1730

Abstract

Bladder cancer is a common cancer; it is the tenth most common cancer in the world. Around one fourth of all diagnosed patients have muscle-invasive bladder cancer (MIBC), characterized by advanced tumors and which remains a lethal disease. The standard treatment for MIBC is the bladder removal by surgery. However, bladder-preserving alternatives are emerging by combining chemotherapy, radiotherapy and minimal surgery, aiming to increase the patient’s quality of life. The aim of the study was to improve these treatments by investigating a novel approach where in addition to radiotherapy, a receptor, TYRO3, a member of TAM receptor tyrosine kinase family known to be highly expressed on the bladder cancer cells and involved in the control of cell survival is targeted. For this, we evaluated the influence of TYRO3 expression levels on a colony or cell survival assays, DNA damage, γH2AX foci formation, gene expression profiling and cell cycle regulation, after radiation on different bladder cell models. We found that TYRO3 expression impacts the radiation response via the cell cycle dysregulation with noeffets on the DNA repair. Therefore, targeting TYRO3 is a promising sensitization marker that could be clinically employed in future treatments. Full article

(This article belongs to the Special Issue Challenges of Radiation Biology for Cancer Management)

► Show Figures

Figure 1

15 pages, 1979 KiB

Open AccessArticle

MicroRNA-29a Manifests Multifaceted Features to Intensify Radiosensitivity, Escalate Apoptosis, and Revoke Cell Migration for Palliating Radioresistance-Enhanced Cervical Cancer Progression

by Pei-Chin Chuang, Ping-Tsung Chen, Chih-Chi Wang, Wen-Hong Su, Yen-Hao Chen and Eng-Yen Huang

Int. J. Mol. Sci. 2022, 23(10), 5524; https://doi.org/10.3390/ijms23105524 - 15 May 2022

Cited by 7 | Viewed by 1899

Abstract

Radioresistance remains a major clinical challenge in cervical cancer therapy and results in tumor relapse and metastasis. Nevertheless, the detailed mechanisms are still largely enigmatic. This study was conducted to elucidate the prospective impacts of microRNA-29a (miR-29a) on the modulation of radioresistance-associated cervical cancer progression. Herein, we established two pairs of parental wild-type (WT) and radioresistant (RR) cervical cancer cells (CaSki and C33A), and we found that constant suppressed miR-29a, but not miR-29b/c, was exhibited in RR-clones that underwent a dose of 6-Gy radiation treatment. Remarkably, radioresistant clones displayed low radiosensitivity, and the reduced apoptosis rate resulted in augmented surviving fractions, measured by the clonogenic survival curve assay and the Annexin V/Propidium Iodide apoptosis assay, respectively. Overexpression of miR-29a effectively intensified the radiosensitivity and triggered the cell apoptosis in RR-clones. In contrast, suppressed miR-29a modestly abridged the radiosensitivity and abolished the cell apoptosis in WT-clones. Hence, ectopically introduced miR-29a into RR-clones notably attenuated the wound-healing rate and cell migration, whereas reduced miR-29a aggravated cell mobilities of WT-clones estimated via the in vitro wound-healing assay and time-lapse recording assay. Notably, we further established the in vivo short-term lung locomotion metastasis model in BALB/c nude mice, and we found that increased lung localization was shown after tail-vein injection of RR-CaSki cells compared to those of WT-CaSki cells. Amplified miR-29a significantly eliminated the radioresistance-enhanced lung locomotion. Our data provide evidence suggesting that miR-29a is a promising microRNA signature in radioresistance of cervical cancer cells and displays multifaceted innovative roles involved in anti-radioresistance, escalated apoptosis, and anti-cell migration/metastasis. Amalgamation of a nucleoid-based strategy (miR-29a) together with conventional radiotherapy may be an innovative and eminent strategy to intensify the radiosensitivity and further protect against the subsequent radioresistance and the potential metastasis in cervical cancer treatment. Full article

(This article belongs to the Special Issue Challenges of Radiation Biology for Cancer Management)

► Show Figures

Figure 1

18 pages, 4075 KiB

Open AccessArticle

Dose Rate Effects on the Selective Radiosensitization of Prostate Cells by GRPR-Targeted Gold Nanoparticles

by Ana Marques, Ana Belchior, Francisco Silva, Fernanda Marques, Maria Paula Cabral Campello, Teresa Pinheiro, Pedro Santos, Luis Santos, António P. A. Matos and António Paulo

Int. J. Mol. Sci. 2022, 23(9), 5279; https://doi.org/10.3390/ijms23095279 - 09 May 2022

Cited by 5 | Viewed by 2198

Abstract

For a while, gold nanoparticles (AuNPs) have been recognized as potential radiosensitizers in cancer radiation therapy, mainly due to their physical properties, making them appealing for medical applications. Nevertheless, the performance of AuNPs as radiosensitizers still raises important questions that need further investigation. Searching for selective prostate (PCa) radiosensitizing agents, we studied the radiosensitization capability of the target-specific AuNP-BBN in cancer versus non-cancerous prostate cells, including the evaluation of dose rate effects in comparison with non-targeted counterparts (AuNP-TDOTA). PCa cells were found to exhibit increased AuNP uptake when compared to non-tumoral ones, leading to a significant loss of cellular proliferation ability and complex DNA damage, evidenced by the occurrence of multiple micronucleus per binucleated cell, in the case of PC3 cells irradiated with 2 Gy of γ-rays, after incubation with AuNP-BBN. Remarkably, the treatment of the PC3 cells with AuNP-BBN led to a much stronger influence of the dose rate on the cellular survival upon γ-photon irradiation, as well as on their genomic instability. Overall, AuNP-BBN emerged in this study as a very promising nanotool for the efficient and selective radiosensitization of human prostate cancer PC3 cells, therefore deserving further preclinical evaluation in adequate animal models for prostate cancer radiotherapy. Full article

(This article belongs to the Special Issue Challenges of Radiation Biology for Cancer Management)

► Show Figures

Figure 1

18 pages, 6755 KiB

Open AccessArticle

1-Isobutanoil-2-isopropylisothiourea Phosphate, T1082: A Safe and Effective Prevention of Radiotherapy Complications in Oncology

by Marina Filimonova, Alina Saburova, Ljudmila Shevchenko, Victoria Makarchuk, Anna Shitova, Olga Soldatova, Vitaly Rybachuk, Alexander Kosachenko, Kirill Nikolaev, Grigory Demyashkin, Vyacheslav Saburov, Sergey Koryakin, Petr Shegay, Andrey Kaprin, Sergey Ivanov and Alexander Filimonov

Int. J. Mol. Sci. 2022, 23(5), 2697; https://doi.org/10.3390/ijms23052697 - 28 Feb 2022

Cited by 1 | Viewed by 2109

Abstract

The radioprotective effects of a new 1-isobutanoil-2-isopropylisothiourea derivative named T1082 are presented. Research methods included toxic characteristics, radioprotective activity (Till–McCulloch’s test and 30-day survival test) in γ-ray total-body-irradiated mice, and a clinical and histological study of the effect of T1082 on acute radiation skin reactions (RSR) in rats after a single or fractionated β-ray local irradiation. T1082 is more effective than its analogue, the NOS inhibitor T1023, at low concentrations and doses (1/12–1/8 LD₁₀), both parenterally and intragastrically. In this case, its therapeutic index (LD₅₀/ED₅₀) reaches 30, and the optimal radioprotective doses (ED_84–98—141–224 mg/kg) are an order less than the maximum tolerated doses—1/16–1/10 LD₁₀. These properties allowed T1082, at a low intragastrical dose (160 mg/kg; 1/14 LD10), to significantly limit the severity of acute RSR after single (40 Gy) and fractionated (78 Gy) β-ray irradiation. The results confirm T1082 as one of the safest emergency radioprotectors and indicate the prospects for its further development as a pharmacological agent for the prevention of RT complications. Full article

(This article belongs to the Special Issue Challenges of Radiation Biology for Cancer Management)

► Show Figures

Figure 1

13 pages, 1903 KiB

Open AccessArticle

CD44, γ-H2AX, and p-ATM Expressions in Short-Term Ex Vivo Culture of Tumour Slices Predict the Treatment Response in Patients with Oral Squamous Cell Carcinoma

by Pierre Philouze, Arnaud Gauthier, Alexandra Lauret, Céline Malesys, Giovanna Muggiolu, Sylvie Sauvaigo, Antoine Galmiche, Philippe Ceruse, Gersende Alphonse, Anne-Sophie Wozny and Claire Rodriguez-Lafrasse

Int. J. Mol. Sci. 2022, 23(2), 877; https://doi.org/10.3390/ijms23020877 - 14 Jan 2022

Cited by 3 | Viewed by 2020

Abstract

Squamous cell carcinoma is the most common type of head and neck cancer (HNSCC) with a disease-free survival at 3 years that does not exceed 30%. Biomarkers able to predict clinical outcomes are clearly needed. The purpose of this study was to investigate whether a short-term culture of tumour fragments irradiated ex vivo could anticipate patient responses to chemo- and/or radiotherapies. Biopsies were collected prior to treatment from a cohort of 28 patients with non-operable tumours of the oral cavity or oropharynx, and then cultured ex vivo. Short-term biopsy slice culture is a robust method that keeps cells viable for 7 days. Different biomarkers involved in the stemness status (CD44) or the DNA damage response (pATM and γ-H2AX) were investigated for their potential to predict the treatment response. A higher expression of all these markers was predictive of a poor response to treatment. This allowed the stratification of responder or non-responder patients to treatment. Moreover, the ratio for the expression of the three markers 24 h after 4 Gy irradiation versus 0 Gy was higher in responder than in non-responder patients. Finally, combining these biomarkers greatly improved their predictive potential, especially when the γ-H2AX ratio was associated with the CD44 ratio or the pATM ratio. These results encourage further evaluation of these biomarkers in a larger cohort of patients. Full article

(This article belongs to the Special Issue Challenges of Radiation Biology for Cancer Management)

► Show Figures

Figure 1

10 pages, 3115 KiB

Open AccessArticle

No Intercellular Regulation of the Cell Cycle among Human Cervical Carcinoma HeLa Cells Expressing Fluorescent Ubiquitination-Based Cell-Cycle Indicators in Modulated Radiation Fields

by Hisanori Fukunaga, Kiichi Kaminaga, Eri Hirose, Ritsuko Watanabe, Noriko Usami, Kevin M. Prise and Akinari Yokoya

Int. J. Mol. Sci. 2021, 22(23), 12785; https://doi.org/10.3390/ijms222312785 - 26 Nov 2021

Cited by 2 | Viewed by 1767

Abstract

The non-targeted effects of radiation have been known to induce significant alternations in cell survival. Although the effects might govern the progression of tumor sites following advanced radiotherapy, the impacts on the intercellular control of the cell cycle following radiation exposure with a modified field, remain to be determined. Recently, a fluorescent ubiquitination-based cell-cycle indicator (FUCCI), which can visualize the cell-cycle phases with fluorescence microscopy in real time, was developed for biological cell research. In this study, we investigated the non-targeted effects on the regulation of the cell cycle of human cervical carcinoma (HeLa) cells with imperfect p53 function that express the FUCCI (HeLa–FUCCI cells). The possible effects on the cell-cycle phases via soluble factors were analyzed following exposure to different field configurations, which were delivered using a 150 kVp X-ray irradiator. In addition, using synchrotron-generated, 5.35 keV monochromatic X-ray microbeams, high-precision 200 μm-slit microbeam irradiation was performed to investigate the possible impacts on the cell-cycle phases via cell–cell contacts. Collectively, we could not detect the intercellular regulation of the cell cycle in HeLa–FUCCI cells, which suggested that the unregulated cell growth was a malignant tumor. Our findings indicated that there was no significant intercellular control system of the cell cycle in malignant tumors during or after radiotherapy, highlighting the differences between normal tissue and tumor characteristics. Full article

(This article belongs to the Special Issue Challenges of Radiation Biology for Cancer Management)

► Show Figures

Figure 1

Review

Jump to: Research

21 pages, 1319 KiB

Open AccessReview

Magnetic-Based Human Tissue 3D Cell Culture: A Systematic Review

by Inês Alexandra Marques, Carolina Fernandes, Nuno Tiago Tavares, Ana Salomé Pires, Ana Margarida Abrantes and Maria Filomena Botelho

Int. J. Mol. Sci. 2022, 23(20), 12681; https://doi.org/10.3390/ijms232012681 - 21 Oct 2022

Cited by 5 | Viewed by 3830

Abstract

Cell-based assays, conducted on monolayer (2D) cultured cells, are an unquestionably valuable tool for biomedical research. However, three-dimensional (3D) cell culture models have gained relevance over the last few years due to the advantages of better mimicking the microenvironment and tissue microarchitecture in vivo. Recent magnetic-based 3D (m3D) cell culture systems can be used for this purpose. These systems are based on exposing magnetized cells to magnetic fields by levitation, bioprinting, or ring formation to promote cell aggregation into 3D structures. However, the successful development of these structures is dependent on several methodological characteristics and can be applied to mimic different human tissues. Thus, a systematic review was performed using Medline (via Pubmed), Scopus, and Web of Science (until February 2022) databases to aggregate studies using m3D culture in which human tissues were mimicked. The search generated 3784 records, of which 25 met the inclusion criteria. The usability of these m3D systems for the development of homotypic or heterotypic spheroids with or without scaffolds was explored in these studies. We also explore methodological differences specifically related to the magnetic method. Generally, the development of m3D cultures has been increasing, with bioprinting and levitation systems being the most used to generate homotypic or heterotypic cultures, mainly to mimic the physiology of human tissues, but also to perform therapeutic screening. This systematic review showed that there are areas of research where the application of this method remains barely explored, such as cancer research. Full article

(This article belongs to the Special Issue Challenges of Radiation Biology for Cancer Management)

► Show Figures

Figure 1

21 pages, 1826 KiB

Open AccessReview

The Potential Effect of Lidocaine, Ropivacaine, Levobupivacaine and Morphine on Breast Cancer Pre-Clinical Models: A Systematic Review

by Ana Catarina Matos, Inês Alexandra Marques, Ana Salomé Pires, Ana Valentim, Ana Margarida Abrantes and Maria Filomena Botelho

Int. J. Mol. Sci. 2022, 23(3), 1894; https://doi.org/10.3390/ijms23031894 - 08 Feb 2022

Cited by 7 | Viewed by 3852

Abstract

Breast cancer (BC) is one of the most common types of cancer and the second leading cause of death in women. Local anaesthetics (LAs) and opioids have been shown to influence cancer progression and metastasis formation in several pre-clinical studies. However, their effects do not seem to promote consensus. A systematic review was conducted using the databases Medline (via PubMed), Scopus, and Web of Science (2010 to December 2021). Search terms included “lidocaine”, “ropivacaine”, “levobupivacaine”, “morphine”, “methadone”, “breast cancer”, “breast carcinoma” and “breast neoplasms” in diverse combinations. The search yielded a total of 784 abstracts for initial review, 23 of which met the inclusion criteria. Here we summarise recent studies on the effect of analgesics and LAs on BC cell lines and animal models and in combination with other treatment regimens. The results suggest that local anaesthetics have anti-tumorigenic properties, hence their clinical application holds therapeutic potential. Regarding morphine, the findings are conflicting, but this opioid appears to be a tumour-promoting agent. Methadone-related results are scarce. Additional research is clearly required to further study the mechanisms underlying the controversial effects of each analgesic or LA to establish the implications upon the outcome and prognosis of BC patients’ treatment. Full article

(This article belongs to the Special Issue Challenges of Radiation Biology for Cancer Management)

► Show Figures