Special Issue "Radiation-Induced Carcinogenesis"

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (15 September 2017)

Special Issue Editors

Guest Editor
Prof. Dr. Alexandros G. Georgakilas

DNA Damage Laboratory, Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens, Zografou Campus, 15780 Athens, Greece
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Fax: +30 210 772 3025
Interests: radiation biology; cancer biology; DNA damage and repair; oxidative stress; carcinogenesis
Guest Editor
Prof. Dr. Lembit Shiver

EBG MedAustron GmbH: Head of Applied Medical Physics Research, Prof. of Medical Rad. Physics with Specialization in Ion Therapy, Head of Radiation Physics, TU Wien-Atominstitut, Stadionallee 2, 1020 Wien, Österreich, Austria
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Phone: +43-2622-26100-950
Interests: radiation therapy; ion therapy; proton therapy; transport simulations; Monte Carlo; DNA damage

Special Issue Information

Dear Colleagues,

Ionizing radiation and related effects in the cell, such as protein, lipid, and DNA damage, are considered as the initial events leading to radiation detrimental effects. Unrepaired or misrepaired damage can lead to mutagenesis, inactivation of DNA damage response pathways, epigenetic changes, and, further, more importantly, genomic instability and malignant transformation. Radiation-induced carcinogenesis is a multi-component function of high-interest to physicists, biologists, and clinicians dealing with radiation-induced secondary cancers. All these fields including the field of non-targeted effects have gained through the years an increased attention. It is of great necessity to clarify and underline the significance and ‘real’ relevance of the initial types of DNA, lipid and/or protein damage in the initiation of carcinogenesis especially at low doses. We would like to invite manuscripts that aim to elucidate the role(s) of radiation-related DNA damage of all forms in primary and secondary carcinogenesis and for various types of cancers like breast, brain, leukemia, lung, prostate, etc. We are particularly interested in manuscripts deciphering the physical and biological mechanisms and pathways that complex DNA damage can lead to mutation and inactivation of DNA repair and apoptotic genes, as well as epigenetic changes and new detection tools. We are also welcome manuscripts focusing on the synergistic effects between inflammation, radiation stress and tumorigenesis in humans and to potential natural anti-inflammatory products that reduce radiation-related cancer risk. New insights gained by the use of omics like genomics, lipidomics, proteomics, as well as theoretical Monte Carlo simulations and modelling, are also welcomed. By devoting a Special Issue to radiation-related carcinogenesis, we hope to join forces and enhance the knowledge in the specific field and above all promote the new era of therapeutic discoveries (like protons) targeting and minimizing radiation-induced adverse effects through the mitigation of harmful radiation effects, especially at the systems biology level.

Assoc. Prof. Dr. Alexandros G. Georgakilas
Prof. Dr. Lembit Shiver
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 papers will be 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. Cancers is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). 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

  • Radiation effects
  • DNA damage and repair
  • inflammation and immune response
  • Monte Carlo simulations and Modelling
  • Non-targeted and abscopal effects
  • genomic instability
  • carcinogenesis
  • Omics, radiogenomics

Published Papers (8 papers)

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Research

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Open AccessArticle Integrative Bioinformatic Analysis of Transcriptomic Data Identifies Conserved Molecular Pathways Underlying Ionizing Radiation-Induced Bystander Effects (RIBE)
Cancers 2017, 9(12), 160; https://doi.org/10.3390/cancers9120160
Received: 6 November 2017 / Revised: 18 November 2017 / Accepted: 22 November 2017 / Published: 25 November 2017
Cited by 1 | PDF Full-text (1925 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ionizing radiation-induced bystander effects (RIBE) encompass a number of effects with potential for a plethora of damages in adjacent non-irradiated tissue. The cascade of molecular events is initiated in response to the exposure to ionizing radiation (IR), something that may occur during diagnostic [...] Read more.
Ionizing radiation-induced bystander effects (RIBE) encompass a number of effects with potential for a plethora of damages in adjacent non-irradiated tissue. The cascade of molecular events is initiated in response to the exposure to ionizing radiation (IR), something that may occur during diagnostic or therapeutic medical applications. In order to better investigate these complex response mechanisms, we employed a unified framework integrating statistical microarray analysis, signal normalization, and translational bioinformatics functional analysis techniques. This approach was applied to several microarray datasets from Gene Expression Omnibus (GEO) related to RIBE. The analysis produced lists of differentially expressed genes, contrasting bystander and irradiated samples versus sham-irradiated controls. Furthermore, comparative molecular analysis through BioInfoMiner, which integrates advanced statistical enrichment and prioritization methodologies, revealed discrete biological processes, at the cellular level. For example, the negative regulation of growth, cellular response to Zn2+-Cd2+, and Wnt and NIK/NF-kappaB signaling, thus refining the description of the phenotypic landscape of RIBE. Our results provide a more solid understanding of RIBE cell-specific response patterns, especially in the case of high-LET radiations, like α-particles and carbon-ions. Full article
(This article belongs to the Special Issue Radiation-Induced Carcinogenesis)
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Open AccessArticle Radiation-Induced Changes of microRNA Expression Profiles in Radiosensitive and Radioresistant Leukemia Cell Lines with Different Levels of Chromosome Abnormalities
Cancers 2017, 9(10), 136; https://doi.org/10.3390/cancers9100136
Received: 14 September 2017 / Revised: 7 October 2017 / Accepted: 10 October 2017 / Published: 13 October 2017
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Abstract
In our study, we estimate an effect from chromosome aberrations and genome mutations on changes in microRNA expression profiles in cancer cell lines demonstrating different radiosensitivity. Here, cell viability and microRNA spectrum have been estimated 1, 4, and 24 h after irradiation. MiSeq [...] Read more.
In our study, we estimate an effect from chromosome aberrations and genome mutations on changes in microRNA expression profiles in cancer cell lines demonstrating different radiosensitivity. Here, cell viability and microRNA spectrum have been estimated 1, 4, and 24 h after irradiation. MiSeq high-throughput sequencing system (Illumina, San Diego, CA, USA) is employed to perform microRNA spectrum estimation. In the K562 cell line, the number of expressed microRNAs in chromosomes demonstrates a more pronounced variation. An analysis of microRNA effects on signaling pathway activity demonstrates differences in post-transcriptional regulation of the expression of genes included into 40 signaling pathways. In the K562 cell line, microRNA dynamics analyzed for their dependence on chromosome localization show a wider scattering of microRNA expression values for a pair of chromosomes compared to the HL-60 cell line. An analysis of microRNAs expression in the K562 and HL-60 cell lines after irradiation has shown that chromosome abnormalities can affect microRNA expression changes. A study of radiation-induced changes of microRNA expression profiles in the K562 and HL-60 cell lines has revealed a dependence of microRNA expression changes on the number of chromosome aberrations and genome mutations. Full article
(This article belongs to the Special Issue Radiation-Induced Carcinogenesis)
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Graphical abstract

Open AccessFeature PaperArticle Predicting Organ-Specific Risk Interactions between Radiation and Chemotherapy in Secondary Cancer Survivors
Received: 6 July 2017 / Revised: 29 August 2017 / Accepted: 4 September 2017 / Published: 6 September 2017
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Abstract
Several studies have shown that pediatric patients have an increased risk of developing a secondary malignancy several decades after treatment with radiotherapy and chemotherapy. In this work, we use a biologically motivated mathematical formalism to estimate the relative risks of breast, lung and [...] Read more.
Several studies have shown that pediatric patients have an increased risk of developing a secondary malignancy several decades after treatment with radiotherapy and chemotherapy. In this work, we use a biologically motivated mathematical formalism to estimate the relative risks of breast, lung and thyroid cancers in childhood cancer survivors due to concurrent therapy regimen. This model specifically includes possible organ-specific interaction between radiotherapy and chemotherapy. The model predicts relative risks for developing secondary cancers after chemotherapy in breast, lung and thyroid tissues, and compared with the epidemiological data. For a concurrent therapy protocol, our model predicted relative risks of 3.2, 9.3, 4.5 as compared to the clinical data, i.e., 1.4, 8.0, 2.3 for secondary breast, lung and thyroid cancer risks, respectively. The extracted chemotherapy mutation induction rates for breast, lung and thyroid are 10−9, 0.5 × 10−6, 0.9 × 10−7 respectively. We found that there exists no synergistic interaction between radiation and chemotherapy for neither mutation induction nor cell kill in lung tissue, but there is an interaction in cell kill for the breast and thyroid organs. These findings help understand the risks of current clinical protocols and might provide rational guidance to develop future multi-modality treatment protocols to minimize secondary cancer risks. Full article
(This article belongs to the Special Issue Radiation-Induced Carcinogenesis)
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Open AccessArticle The Role of Radiation Induced Injury on Lung Cancer
Received: 1 June 2017 / Revised: 7 July 2017 / Accepted: 8 July 2017 / Published: 12 July 2017
Cited by 3 | PDF Full-text (908 KB) | HTML Full-text | XML Full-text
Abstract
This manuscript evaluates the role of cell killing, tissue disorganization, and tissue damage on the induction of lung cancer following low dose rate radiation exposures from internally deposited radioactive materials. Beagle dogs were exposed by inhalation to 90Y, 91Y, 144Ce, [...] Read more.
This manuscript evaluates the role of cell killing, tissue disorganization, and tissue damage on the induction of lung cancer following low dose rate radiation exposures from internally deposited radioactive materials. Beagle dogs were exposed by inhalation to 90Y, 91Y, 144Ce, or 90Sr in fused clay particles. Dogs lived out their life span with complete pathology conducted at the time of death. The radiation dose per cell turnover was characterized and related to the cause of death for each animal. Large doses per cell turnover resulted in acute death from lung damage with extensive cell killing, tissue disorganization, chronic inflammatory disease, fibrosis, and pneumonitis. Dogs with lower doses per cell turnover developed a very high frequency of lung cancer. As the dose per cell turnover was further decreased, no marked tissue damage and no significant change in either life span or lung cancer frequency was observed. Radiation induced tissue damage and chronic inflammatory disease results in high cancer frequencies in the lung. At doses where a high frequency of chromosome damage and mutations would be predicted to occur there was no decrease in life span or increase in lung cancer. Such research suggests that cell killing and tissue damage and the physiological responses to that damage are important mechanisms in radiation induced lung cancer. Full article
(This article belongs to the Special Issue Radiation-Induced Carcinogenesis)
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Review

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Open AccessReview Recent Advances in Cancer Therapy Based on Dual Mode Gold Nanoparticles
Cancers 2017, 9(12), 173; https://doi.org/10.3390/cancers9120173
Received: 9 October 2017 / Revised: 9 December 2017 / Accepted: 15 December 2017 / Published: 19 December 2017
Cited by 13 | PDF Full-text (644 KB) | HTML Full-text | XML Full-text
Abstract
Many tumor-targeted strategies have been used worldwide to limit the side effects and improve the effectiveness of therapies, such as chemotherapy, radiotherapy (RT), etc. Biophotonic therapy modalities comprise very promising alternative techniques for cancer treatment with minimal invasiveness and side-effects. These modalities use [...] Read more.
Many tumor-targeted strategies have been used worldwide to limit the side effects and improve the effectiveness of therapies, such as chemotherapy, radiotherapy (RT), etc. Biophotonic therapy modalities comprise very promising alternative techniques for cancer treatment with minimal invasiveness and side-effects. These modalities use light e.g., laser irradiation in an extracorporeal or intravenous mode to activate photosensitizer agents with selectivity in the target tissue. Photothermal therapy (PTT) is a minimally invasive technique for cancer treatment which uses laser-activated photoabsorbers to convert photon energy into heat sufficient to induce cells destruction via apoptosis, necroptosis and/or necrosis. During the last decade, PTT has attracted an increased interest since the therapy can be combined with customized functionalized nanoparticles (NPs). Recent advances in nanotechnology have given rise to generation of various types of NPs, like gold NPs (AuNPs), designed to act both as radiosensitizers and photothermal sensitizing agents due to their unique optical and electrical properties i.e., functioning in dual mode. Functionalized AuNPS can be employed in combination with non-ionizing and ionizing radiation to significantly improve the efficacy of cancer treatment while at the same time sparing normal tissues. Here, we first provide an overview of the use of NPs for cancer therapy. Then we review many recent advances on the use of gold NPs in PTT, RT and PTT/RT based on different types of AuNPs, irradiation conditions and protocols. We refer to the interaction mechanisms of AuNPs with cancer cells via the effects of non-ionizing and ionizing radiations and we provide recent existing experimental data as a baseline for the design of optimized protocols in PTT, RT and PTT/RT combined treatment. Full article
(This article belongs to the Special Issue Radiation-Induced Carcinogenesis)
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Open AccessReview Clinical and Functional Assays of Radiosensitivity and Radiation-Induced Second Cancer
Cancers 2017, 9(11), 147; https://doi.org/10.3390/cancers9110147
Received: 22 September 2017 / Revised: 24 October 2017 / Accepted: 24 October 2017 / Published: 27 October 2017
Cited by 5 | PDF Full-text (806 KB) | HTML Full-text | XML Full-text
Abstract
Whilst the near instantaneous physical interaction of radiation energy with living cells leaves little opportunity for inter-individual variation in the initial yield of DNA damage, all the downstream processes in how damage is recognized, repaired or resolved and therefore the ultimate fate of [...] Read more.
Whilst the near instantaneous physical interaction of radiation energy with living cells leaves little opportunity for inter-individual variation in the initial yield of DNA damage, all the downstream processes in how damage is recognized, repaired or resolved and therefore the ultimate fate of cells can vary across the population. In the clinic, this variability is observed most readily as rare extreme sensitivity to radiotherapy with acute and late tissue toxic reactions. Though some radiosensitivity can be anticipated in individuals with known genetic predispositions manifest through recognizable phenotypes and clinical presentations, others exhibit unexpected radiosensitivity which nevertheless has an underlying genetic cause. Currently, functional assays for cellular radiosensitivity represent a strategy to identify patients with potential radiosensitivity before radiotherapy begins, without needing to discover or evaluate the impact of the precise genetic determinants. Yet, some of the genes responsible for extreme radiosensitivity would also be expected to confer susceptibility to radiation-induced cancer, which can be considered another late adverse event associated with radiotherapy. Here, the utility of functional assays of radiosensitivity for identifying individuals susceptible to radiotherapy-induced second cancer is discussed, considering both the common mechanisms and important differences between stochastic radiation carcinogenesis and the range of deterministic acute and late toxic effects of radiotherapy. Full article
(This article belongs to the Special Issue Radiation-Induced Carcinogenesis)
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Open AccessReview Secondary Intracranial Tumors Following Radiotherapy for Pituitary Adenomas: A Systematic Review
Received: 4 June 2017 / Revised: 2 August 2017 / Accepted: 4 August 2017 / Published: 8 August 2017
Cited by 2 | PDF Full-text (6786 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Pituitary adenomas are often treated with radiotherapy for the management of tumor progression or recurrence. Despite the improvement in cure rates, patients treated by radiotherapy are at risk of development of secondary malignancies. We conducted a comprehensive literature review of the secondary intracranial [...] Read more.
Pituitary adenomas are often treated with radiotherapy for the management of tumor progression or recurrence. Despite the improvement in cure rates, patients treated by radiotherapy are at risk of development of secondary malignancies. We conducted a comprehensive literature review of the secondary intracranial tumors that occurred following radiotherapy to pituitary adenomas to obtain clinicopathological characteristics. The analysis included 48 neuroepithelial tumors, 37 meningiomas, and 52 sarcomas which were published between 1959–2017, although data is missing regarding overall survival and type of irradiation in a significant proportion of the reports. The average onset age for the pituitary adenoma was 37.2 ± 14.4 years and the average latency period before the diagnosis of the secondary tumor was 15.2 ± 8.7 years. Radiotherapy was administered in pituitary adenomas at an average dose of 52.0 ± 19.5 Gy. The distribution of pituitary adenomas according to their function was prolactinoma in 10 (7.2%) cases, acromegaly in 37 (27.0%) cases, Cushing disease in 4 (2.9%) cases, PRL+GH in 1 (0.7%) case, non-functioning adenoma in 57 (41.6%) cases. Irradiation technique delivered was lateral opposing field in 23 (16.7%) cases, 3 or 4 field technique in 27 (19.6%) cases, rotation technique in 10 (7.2%) cases, radio surgery in 6 (4.3%) cases. Most of the glioma or sarcoma had been generated after lateral opposing field or 3/4 field technique. Fibrosarcomas were predominant before 1979 (p < 0.0001). The median overall survival time for all neuroepithelial tumors was 11 months (95% confidence intervals (CI), 3–14). Patients with gliomas treated with radiotherapy exhibited a non-significant positive trend with longer overall survival. The median overall survival time for sarcoma cases was 6 months (95% CI, 1.5–9). The median survival time in patients with radiation and/or chemotherapy for sarcomas exhibited a non-significant positive trend with longer overall survival. In patients treated with radiotherapy for pituitary adenomas, the risk of secondary tumor incidence warrants a longer follow up period. Moreover, radiation and/or chemotherapy should be considered in cases of secondary glioma or sarcoma following radiotherapy to the pituitary adenomas. Full article
(This article belongs to the Special Issue Radiation-Induced Carcinogenesis)
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Open AccessReview Complex DNA Damage: A Route to Radiation-Induced Genomic Instability and Carcinogenesis
Received: 26 May 2017 / Revised: 6 July 2017 / Accepted: 14 July 2017 / Published: 18 July 2017
Cited by 22 | PDF Full-text (1537 KB) | HTML Full-text | XML Full-text
Abstract
Cellular effects of ionizing radiation (IR) are of great variety and level, but they are mainly damaging since radiation can perturb all important components of the cell, from the membrane to the nucleus, due to alteration of different biological molecules ranging from lipids [...] Read more.
Cellular effects of ionizing radiation (IR) are of great variety and level, but they are mainly damaging since radiation can perturb all important components of the cell, from the membrane to the nucleus, due to alteration of different biological molecules ranging from lipids to proteins or DNA. Regarding DNA damage, which is the main focus of this review, as well as its repair, all current knowledge indicates that IR-induced DNA damage is always more complex than the corresponding endogenous damage resulting from endogenous oxidative stress. Specifically, it is expected that IR will create clusters of damage comprised of a diversity of DNA lesions like double strand breaks (DSBs), single strand breaks (SSBs) and base lesions within a short DNA region of up to 15–20 bp. Recent data from our groups and others support two main notions, that these damaged clusters are: (1) repair resistant, increasing genomic instability (GI) and malignant transformation and (2) can be considered as persistent “danger” signals promoting chronic inflammation and immune response, causing detrimental effects to the organism (like radiation toxicity). Last but not least, the paradigm shift for the role of radiation-induced systemic effects is also incorporated in this picture of IR-effects and consequences of complex DNA damage induction and its erroneous repair. Full article
(This article belongs to the Special Issue Radiation-Induced Carcinogenesis)
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