Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.8
5.6
Journals
IJMS
Special Issues
Molecular Research in Radiobiology
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Molecular Research in Radiobiology

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 48122

Special Issue Editor

Prof. Dr. Orla L. Howe

E-Mail Website
Guest Editor
School of Biological & Health Sciences, Technological University Dublin, Dublin, Ireland
Interests: radiobiology; novel therpeutics; targeted therapies; cell signalling; molecular biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Radiobiology has significantly impacted science and medicine in the last century, using biological models to study targeted and non-targeted effects of radiation in both cancerous and normal tissue. The use of molecular tools in radiobiology led to discoveries of the DNA damage response (DDR) signaling pathway and further molecular mechanisms of repair, radiosensitivitiy, radioresistance, and biomarkers of radiation response. Translational radiobiology and studies on the tumor microenvironment have provided a deeper understanding of the effects of clinical radiation therapy (RT) fractionation on treatment efficacy by the 5 R’s (Repair, Redistribution, Reoxygenation, Repopulation, and Radiosensitivity), and more recently the reactivation of an anti-tumour response (the 6th R) significant for recent immunotherapy/RT combination regimes. Recent advances in radiobiology can be mainly attributed to rapid molecular and technological advances including omics and systems biology approaches.

This Special Issue, “Molecular Research in Radiobiology,” will cover a selection of recent research topics and current review articles in this area.

Prof. Dr. Orla L. Howe
Guest Editor

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

  • Biomarkers
  • Omics and systems Biology
  • Radiosensitivity/Radioresistance (Radiation modifiers/radiosensitisers)
  • Epigenetics
  • DNA damage/repair
  • Non-targeted effects (genomic instability/Bystander effects)
  • Tumour microenvironment
  • Non-cancer effects
  • Emerging technologies

Related Special Issue

Published Papers (16 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

20 pages, 4241 KiB  
Article
Application of Advanced Non-Linear Spectral Decomposition and Regression Methods for Spectroscopic Analysis of Targeted and Non-Targeted Irradiation Effects in an In-Vitro Model
by Ciara Slattery, Khanh Nguyen, Laura Shields, Isabel Vega-Carrascal, Sean Singleton, Fiona M. Lyng, Brendan McClean and Aidan D. Meade
Int. J. Mol. Sci. 2022, 23(21), 12986; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232112986 - 26 Oct 2022
Cited by 2 | Viewed by 2088
Abstract
Irradiation of the tumour site during treatment for cancer with external-beam ionising radiation results in a complex and dynamic series of effects in both the tumour itself and the normal tissue which surrounds it. The development of a spectral model of the effect [...] Read more.
Irradiation of the tumour site during treatment for cancer with external-beam ionising radiation results in a complex and dynamic series of effects in both the tumour itself and the normal tissue which surrounds it. The development of a spectral model of the effect of each exposure and interaction mode between these tissues would enable label free assessment of the effect of radiotherapeutic treatment in practice. In this study Fourier transform Infrared microspectroscopic imaging was employed to analyse an in-vitro model of radiotherapeutic treatment for prostate cancer, in which a normal cell line (PNT1A) was exposed to low-dose X-ray radiation from the scattered treatment beam, and also to irradiated cell culture medium (ICCM) from a cancer cell line exposed to a treatment relevant dose (2 Gy). Various exposure modes were studied and reference was made to previously acquired data on cellular survival and DNA double strand break damage. Spectral analysis with manifold methods, linear spectral fitting, non-linear classification and non-linear regression approaches were found to accurately segregate spectra on irradiation type and provide a comprehensive set of spectral markers which differentiate on irradiation mode and cell fate. The study demonstrates that high dose irradiation, low-dose scatter irradiation and radiation-induced bystander exposure (RIBE) signalling each produce differential effects on the cell which are observable through spectroscopic analysis. Full article
(This article belongs to the Special Issue Molecular Research in Radiobiology)
►▼ Show Figures

Figure 1

12 pages, 14876 KiB  
Article
Mutation Analysis of Radioresistant Early-Stage Cervical Cancer
by Tae Oike, Yoshihito Sekiguchi, Yuya Yoshimoto, Takahiro Oike, Ken Ando, Wenchao Gu, Yasushi Sasaki, Takashi Tokino, Akira Iwase and Tatsuya Ohno
Int. J. Mol. Sci. 2022, 23(1), 51; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23010051 - 21 Dec 2021
Cited by 3 | Viewed by 2896
Abstract
Radiotherapy is a definitive treatment for early-stage cervical cancer; however, a subset of this disease recurs locally, necessitating establishment of predictive biomarkers and treatment strategies. To address this issue, we performed gene panel-based sequencing of 18 stage IB cervical cancers treated with definitive [...] Read more.
Radiotherapy is a definitive treatment for early-stage cervical cancer; however, a subset of this disease recurs locally, necessitating establishment of predictive biomarkers and treatment strategies. To address this issue, we performed gene panel-based sequencing of 18 stage IB cervical cancers treated with definitive radiotherapy, including two cases of local recurrence, followed by in vitro and in silico analyses. Simultaneous mutations in KRAS and SMAD4 (KRASmt/SMAD4mt) were detected only in a local recurrence case, indicating potential association of this mutation signature with radioresistance. In isogenic cell-based experiments, a combination of activating KRAS mutation and SMAD4 deficiency led to X-ray resistance, whereas either of these factors alone did not. Analysis of genomic data from 55,308 cancers showed a significant trend toward co-occurrence of mutations in KRAS and SMAD4. Gene Set Enrichment Analysis of the Cancer Cell Line Encyclopedia dataset suggested upregulation of the pathways involved in epithelial mesenchymal transition and inflammatory responses in KRASmt/SMAD4mt cancer cells. Notably, irradiation with therapeutic carbon ions led to robust killing of X-ray-resistant KRASmt/SMAD4mt cancer cells. These data indicate that the KRASmt/SMAD4mt signature is a potential predictor of radioresistance, and that carbon ion radiotherapy is a potential option to treat early-stage cervical cancers with the KRASmt/SMAD4mt signature. Full article
(This article belongs to the Special Issue Molecular Research in Radiobiology)
►▼ Show Figures

Figure 1

13 pages, 2797 KiB  
Article
Relationship of In Vitro Toxicity of Technetium-99m to Subcellular Localisation and Absorbed Dose
by Ines M. Costa, Noor Siksek, Alessia Volpe, Francis Man, Katarzyna M. Osytek, Elise Verger, Giuseppe Schettino, Gilbert O. Fruhwirth and Samantha Y. A. Terry
Int. J. Mol. Sci. 2021, 22(24), 13466; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222413466 - 15 Dec 2021
Cited by 4 | Viewed by 3084
Abstract
Auger electron-emitters increasingly attract attention as potential radionuclides for molecular radionuclide therapy in oncology. The radionuclide technetium-99m is widely used for imaging; however, its potential as a therapeutic radionuclide has not yet been fully assessed. We used MDA-MB-231 breast cancer cells engineered to [...] Read more.
Auger electron-emitters increasingly attract attention as potential radionuclides for molecular radionuclide therapy in oncology. The radionuclide technetium-99m is widely used for imaging; however, its potential as a therapeutic radionuclide has not yet been fully assessed. We used MDA-MB-231 breast cancer cells engineered to express the human sodium iodide symporter-green fluorescent protein fusion reporter (hNIS-GFP; MDA-MB-231.hNIS-GFP) as a model for controlled cellular radionuclide uptake. Uptake, efflux, and subcellular location of the NIS radiotracer [99mTc]TcO4− were characterised to calculate the nuclear-absorbed dose using Medical Internal Radiation Dose formalism. Radiotoxicity was determined using clonogenic and γ-H2AX assays. The daughter radionuclide technetium-99 or external beam irradiation therapy (EBRT) served as controls. [99mTc]TcO4− in vivo biodistribution in MDA-MB-231.hNIS-GFP tumour-bearing mice was determined by imaging and complemented by ex vivo tissue radioactivity analysis. [99mTc]TcO4− resulted in substantial DNA damage and reduction in the survival fraction (SF) following 24 h incubation in hNIS-expressing cells only. We found that 24,430 decays/cell (30 mBq/cell) were required to achieve SF0.37 (95%-confidence interval = [SF0.31; SF0.43]). Different approaches for determining the subcellular localisation of [99mTc]TcO4− led to SF0.37 nuclear-absorbed doses ranging from 0.33 to 11.7 Gy. In comparison, EBRT of MDA-MB-231.hNIS-GFP cells resulted in an SF0.37 of 2.59 Gy. In vivo retention of [99mTc]TcO4− after 24 h remained high at 28.0% ± 4.5% of the administered activity/gram tissue in MDA-MB-231.hNIS-GFP tumours. [99mTc]TcO4− caused DNA damage and reduced clonogenicity in this model, but only when the radioisotope was taken up into the cells. This data guides the safe use of technetium-99m during imaging and potential future therapeutic applications. Full article
(This article belongs to the Special Issue Molecular Research in Radiobiology)
►▼ Show Figures

Graphical abstract

22 pages, 2997 KiB  
Article
Long-Term Sex- and Genotype-Specific Effects of 56Fe Irradiation on Wild-Type and APPswe/PS1dE9 Transgenic Mice
by Maren K. Schroeder, Bin Liu, Robert G. Hinshaw, Mi-Ae Park, Shuyan Wang, Shipra Dubey, Grace Geyu Liu, Qiaoqiao Shi, Peter Holton, Vladimir Reiser, Paul A. Jones, William Trigg, Marcelo F. Di Carli, Barbara J. Caldarone, Jacqueline P. Williams, M. Kerry O’Banion and Cynthia A. Lemere
Int. J. Mol. Sci. 2021, 22(24), 13305; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222413305 - 10 Dec 2021
Cited by 9 | Viewed by 2502
Abstract
Space radiation presents a substantial threat to travel beyond Earth. Relatively low doses of high-energy particle radiation cause physiological and behavioral impairments in rodents and may pose risks to human spaceflight. There is evidence that 56Fe irradiation, a significant component of space [...] Read more.
Space radiation presents a substantial threat to travel beyond Earth. Relatively low doses of high-energy particle radiation cause physiological and behavioral impairments in rodents and may pose risks to human spaceflight. There is evidence that 56Fe irradiation, a significant component of space radiation, may be more harmful to males than to females and worsen Alzheimer’s disease pathology in genetically vulnerable models. Yet, research on the long-term, sex- and genotype-specific effects of 56Fe irradiation is lacking. Here, we irradiated 4-month-old male and female, wild-type and Alzheimer’s-like APP/PS1 mice with 0, 0.10, or 0.50 Gy of 56Fe ions (1GeV/u). Mice underwent microPET scans before and 7.5 months after irradiation, a battery of behavioral tests at 11 months of age and were sacrificed for pathological and biochemical analyses at 12 months of age. 56Fe irradiation worsened amyloid-beta (Aβ) pathology, gliosis, neuroinflammation and spatial memory, but improved motor coordination, in male transgenic mice and worsened fear memory in wild-type males. Although sham-irradiated female APP/PS1 mice had more cerebral Aβ and gliosis than sham-irradiated male transgenics, female mice of both genotypes were relatively spared from radiation effects 8 months later. These results provide evidence for sex-specific, long-term CNS effects of space radiation. Full article
(This article belongs to the Special Issue Molecular Research in Radiobiology)
►▼ Show Figures

Figure 1

20 pages, 2384 KiB  
Article
Long-Term Effects of Ionizing Radiation on the Hippocampus: Linking Effects of the Sonic Hedgehog Pathway Activation with Radiation Response
by Francesca Antonelli, Arianna Casciati, Montserrat Belles, Noemi Serra, Maria Victoria Linares-Vidal, Carmela Marino, Mariateresa Mancuso and Simonetta Pazzaglia
Int. J. Mol. Sci. 2021, 22(22), 12605; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212605 - 22 Nov 2021
Cited by 4 | Viewed by 2477
Abstract
Radiation therapy represents one of the primary treatment modalities for primary and metastatic brain tumors. Although recent advances in radiation techniques, that allow the delivery of higher radiation doses to the target volume, reduce the toxicity to normal tissues, long-term neurocognitive decline is [...] Read more.
Radiation therapy represents one of the primary treatment modalities for primary and metastatic brain tumors. Although recent advances in radiation techniques, that allow the delivery of higher radiation doses to the target volume, reduce the toxicity to normal tissues, long-term neurocognitive decline is still a detrimental factor significantly affecting quality of life, particularly in pediatric patients. This imposes the need for the development of prevention strategies. Based on recent evidence, showing that manipulation of the Shh pathway carries therapeutic potential for brain repair and functional recovery after injury, here we evaluate how radiation-induced hippocampal alterations are modulated by the constitutive activation of the Shh signaling pathway in Patched 1 heterozygous mice (Ptch1+/−). Our results show, for the first time, an overall protective effect of constitutive Shh pathway activation on hippocampal radiation injury. This activation, through modulation of the proneural gene network, leads to a long-term reduction of hippocampal deficits in the stem cell and new neuron compartments and to the mitigation of radio-induced astrogliosis, despite some behavioral alterations still being detected in Ptch1+/− mice. A better understanding of the pathogenic mechanisms responsible for the neural decline following irradiation is essential for identifying prevention measures to contain the harmful consequences of irradiation. Our data have important translational implications as they suggest a role for Shh pathway manipulation to provide the therapeutic possibility of improving brain repair and functional recovery after radio-induced injury. Full article
(This article belongs to the Special Issue Molecular Research in Radiobiology)
►▼ Show Figures

Figure 1

25 pages, 3684 KiB  
Article
Ionising Radiation Promotes Invasive Potential of Breast Cancer Cells: The Role of Exosomes in the Process
by Raheem AL-Abedi, Seda Tuncay Cagatay, Ammar Mayah, Susan A. Brooks and Munira Kadhim
Int. J. Mol. Sci. 2021, 22(21), 11570; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111570 - 26 Oct 2021
Cited by 17 | Viewed by 2640
Abstract
Along with the cells that are exposed to radiation, non-irradiated cells can unveil radiation effects as a result of intercellular communication, which are collectively defined as radiation induced bystander effects (RIBE). Exosome-mediated signalling is one of the core mechanisms responsible for multidirectional communication [...] Read more.
Along with the cells that are exposed to radiation, non-irradiated cells can unveil radiation effects as a result of intercellular communication, which are collectively defined as radiation induced bystander effects (RIBE). Exosome-mediated signalling is one of the core mechanisms responsible for multidirectional communication of tumor cells and their associated microenvironment, which may result in enhancement of malignant tumor phenotypes. Recent studies show that exosomes and exosome-mediated signalling also play a dynamic role in RIBE in cancer cell lines, many of which focused on altered exosome cargo or their effects on DNA damage. However, there is a lack of knowledge regarding how these changes in exosome cargo are reflected in other functional characteristics of cancer cells from the aspects of invasiveness and metastasis. Therefore, in the current study, we aimed to investigate exosome-mediated bystander effects of 2 Gy X-ray therapeutic dose of ionizing radiation on the invasive potential of MCF-7 breast cancer cells in vitro via assessing Matrigel invasion potential, epithelial mesenchymal transition (EMT) characteristics and the extent of glycosylation, as well as underlying plausible molecular mechanisms. The findings show that exosomes derived from irradiated MCF-7 cells enhance invasiveness of bystander MCF-7 cells, possibly through altered miRNA and protein content carried in exosomes. Full article
(This article belongs to the Special Issue Molecular Research in Radiobiology)
►▼ Show Figures

Figure 1

16 pages, 3184 KiB  
Article
Gut Microbiota-Derived l-Histidine/Imidazole Propionate Axis Fights against the Radiation-Induced Cardiopulmonary Injury
by Zhiyuan Chen, Bin Wang, Jiali Dong, Yuan Li, Shuqin Zhang, Xiaozhou Zeng, Huiwen Xiao, Saijun Fan and Ming Cui
Int. J. Mol. Sci. 2021, 22(21), 11436; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111436 - 23 Oct 2021
Cited by 18 | Viewed by 3479
Abstract
Radiation-induced cardiopulmonary injuries are the most common and intractable side effects that are entwined with radiotherapy for thorax cancers. However, the therapeutic options for such complications have yielded disappointing results in clinical applications. Here, we reported that gut microbiota-derived l-Histidine and its [...] Read more.
Radiation-induced cardiopulmonary injuries are the most common and intractable side effects that are entwined with radiotherapy for thorax cancers. However, the therapeutic options for such complications have yielded disappointing results in clinical applications. Here, we reported that gut microbiota-derived l-Histidine and its secondary metabolite imidazole propionate (ImP) fought against radiation-induced cardiopulmonary injury in an entiric flora-dependent manner in mouse models. Local chest irradiation decreased the level of l-Histidine in fecal pellets, which was increased following fecal microbiota transplantation. l-Histidine replenishment via an oral route retarded the pathological process of lung and heart tissues and improved lung respiratory and heart systolic function following radiation exposure. l-Histidine preserved the gut bacterial taxonomic proportions shifted by total chest irradiation but failed to perform radioprotection in gut microbiota-deleted mice. ImP, the downstream metabolite of l-Histidine, accumulated in peripheral blood and lung tissues following l-Histidine replenishment and protected against radiation-induced lung and heart toxicity. Orally gavaged ImP could not enter into the circulatory system in mice through an antibiotic cocktail treatment. Importantly, ImP inhibited pyroptosis to nudge lung cell proliferation after radiation challenge. Together, our findings pave a novel method of protection against cardiopulmonary complications intertwined with radiotherapy in pre-clinical settings and underpin the idea that gut microbiota-produced l-Histidine and ImP are promising radioprotective agents. Full article
(This article belongs to the Special Issue Molecular Research in Radiobiology)
►▼ Show Figures

Figure 1

18 pages, 3894 KiB  
Article
A 4-Gene Signature of CDKN1, FDXR, SESN1 and PCNA Radiation Biomarkers for Prediction of Patient Radiosensitivity
by Orla Howe, Lisa White, Daniel Cullen, Grainne O’Brien, Laura Shields, Jane Bryant, Emma Noone, Shirley Bradshaw, Marie Finn, Mary Dunne, Aoife M. Shannon, John Armstrong, Brendan McClean, Aidan Meade, Christophe Badie and Fiona M. Lyng
Int. J. Mol. Sci. 2021, 22(19), 10607; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910607 - 30 Sep 2021
Cited by 3 | Viewed by 1955
Abstract
The quest for the discovery and validation of radiosensitivity biomarkers is ongoing and while conventional bioassays are well established as biomarkers, molecular advances have unveiled new emerging biomarkers. Herein, we present the validation of a new 4-gene signature panel of CDKN1, FDXR, SESN1 [...] Read more.
The quest for the discovery and validation of radiosensitivity biomarkers is ongoing and while conventional bioassays are well established as biomarkers, molecular advances have unveiled new emerging biomarkers. Herein, we present the validation of a new 4-gene signature panel of CDKN1, FDXR, SESN1 and PCNA previously reported to be radiation-responsive genes, using the conventional G2 chromosomal radiosensitivity assay. Radiation-induced G2 chromosomal radiosensitivity at 0.05 Gy and 0.5 Gy IR is presented for a healthy control (n = 45) and a prostate cancer (n = 14) donor cohort. For the prostate cancer cohort, data from two sampling time points (baseline and Androgen Deprivation Therapy (ADT)) is provided, and a significant difference (p > 0.001) between 0.05 Gy and 0.5 Gy was evident for all donor cohorts. Selected donor samples from each cohort also exposed to 0.05 Gy and 0.5 Gy IR were analysed for relative gene expression of the 4-gene signature. In the healthy donor cohort, there was a significant difference in gene expression between IR dose for CDKN1, FXDR and SESN1 but not PCNA and no significant difference found between all prostate cancer donors, unless they were classified as radiation-induced G2 chromosomal radiosensitive. Interestingly, ADT had an effect on radiation response for some donors highlighting intra-individual heterogeneity of prostate cancer donors. Full article
(This article belongs to the Special Issue Molecular Research in Radiobiology)
►▼ Show Figures

Figure 1

15 pages, 4028 KiB  
Article
Deciphering Differential Life Stage Radioinduced Reproductive Decline in Caenorhabditis elegans through Lipid Analysis
by Elizabeth Dufourcq-Sekatcheff, Stephan Cuiné, Yonghua Li-Beisson, Loïc Quevarec, Myriam Richaud, Simon Galas and Sandrine Frelon
Int. J. Mol. Sci. 2021, 22(19), 10277; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910277 - 24 Sep 2021
Cited by 5 | Viewed by 1904
Abstract
Wildlife is chronically exposed to various sources of ionizing radiations, both environmental or anthropic, due to nuclear energy use, which can induce several defects in organisms. In invertebrates, reproduction, which directly impacts population dynamics, has been found to be the most radiosensitive endpoint. [...] Read more.
Wildlife is chronically exposed to various sources of ionizing radiations, both environmental or anthropic, due to nuclear energy use, which can induce several defects in organisms. In invertebrates, reproduction, which directly impacts population dynamics, has been found to be the most radiosensitive endpoint. Understanding the underlying molecular pathways inducing this reproduction decrease can help in predicting the effects at larger scales (i.e., population). In this study, we used a life stage dependent approach in order to better understand the molecular determinants of reproduction decrease in the roundworm C. elegans. Worms were chronically exposed to 50 mGy·h−1 external gamma ionizing radiations throughout different developmental periods (namely embryogenesis, gametogenesis, and full development). Then, in addition to reproduction parameters, we performed a wide analysis of lipids (different class and fatty acid via FAMES), which are both important signaling molecules for reproduction and molecular targets of oxidative stress. Our results showed that reproductive defects are life stage dependent, that lipids are differently misregulated according to the considered exposure (e.g., upon embryogenesis and full development) and do not fully explain radiation induced reproductive defects. Finally, our results enable us to propose a conceptual model of lipid signaling after radiation stress in which both the soma and the germline participate. Full article
(This article belongs to the Special Issue Molecular Research in Radiobiology)
►▼ Show Figures

Figure 1

18 pages, 1679 KiB  
Article
Lipid Droplet Biosynthesis Impairment through DGAT2 Inhibition Sensitizes MCF7 Breast Cancer Cells to Radiation
by Clelia Nisticò, Francesca Pagliari, Emanuela Chiarella, Joana Fernandes Guerreiro, Maria Grazia Marafioti, Ilenia Aversa, Geraldine Genard, Rachel Hanley, Daniel Garcia-Calderón, Heather Mandy Bond, Maria Mesuraca, Luca Tirinato, Maria Francesca Spadea and Joao Carlos Seco
Int. J. Mol. Sci. 2021, 22(18), 10102; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221810102 - 18 Sep 2021
Cited by 25 | Viewed by 4220
Abstract
Breast cancer is the most frequent cancer in women worldwide and late diagnosis often adversely affects the prognosis of the disease. Radiotherapy is commonly used to treat breast cancer, reducing the risk of recurrence after surgery. However, the eradication of radioresistant cancer cells, [...] Read more.
Breast cancer is the most frequent cancer in women worldwide and late diagnosis often adversely affects the prognosis of the disease. Radiotherapy is commonly used to treat breast cancer, reducing the risk of recurrence after surgery. However, the eradication of radioresistant cancer cells, including cancer stem cells, remains the main challenge of radiotherapy. Recently, lipid droplets (LDs) have been proposed as functional markers of cancer stem cells, also being involved in increased cell tumorigenicity. LD biogenesis is a multistep process requiring various enzymes, including Diacylglycerol acyltransferase 2 (DGAT2). In this context, we evaluated the effect of PF-06424439, a selective DGAT2 inhibitor, on MCF7 breast cancer cells exposed to X-rays. Our results demonstrated that 72 h of PF-06424439 treatment reduced LD content and inhibited cell migration, without affecting cell proliferation. Interestingly, PF-06424439 pre-treatment followed by radiation was able to enhance radiosensitivity of MCF7 cells. In addition, the combined treatment negatively interfered with lipid metabolism-related genes, as well as with EMT gene expression, and modulated the expression of typical markers associated with the CSC-like phenotype. These findings suggest that PF-06424439 pre-treatment coupled to X-ray exposure might potentiate breast cancer cell radiosensitivity and potentially improve the radiotherapy effectiveness. Full article
(This article belongs to the Special Issue Molecular Research in Radiobiology)
►▼ Show Figures

Graphical abstract

17 pages, 7018 KiB  
Article
High-Dose Irradiation Inhibits Motility and Induces Autophagy in Caenorhabditis elegans
by Akira Yamasaki, Michiyo Suzuki, Tomoo Funayama, Takahito Moriwaki, Tetsuya Sakashita, Yasuhiko Kobayashi and Qiu-Mei Zhang-Akiyama
Int. J. Mol. Sci. 2021, 22(18), 9810; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22189810 - 10 Sep 2021
Cited by 3 | Viewed by 3133
Abstract
Radiation damages many cellular components and disrupts cellular functions, and was previously reported to impair locomotion in the model organism Caenorhabditis elegans. However, the response to even higher doses is not clear. First, to investigate the effects of high-dose radiation on the [...] Read more.
Radiation damages many cellular components and disrupts cellular functions, and was previously reported to impair locomotion in the model organism Caenorhabditis elegans. However, the response to even higher doses is not clear. First, to investigate the effects of high-dose radiation on the locomotion of C. elegans, we investigated the dose range that reduces whole-body locomotion or leads to death. Irradiation was performed in the range of 0–6 kGy. In the crawling analysis, motility decreased after irradiation in a dose-dependent manner. Exposure to 6 kGy of radiation affected crawling on agar immediately and caused the complete loss of motility. Both γ-rays and carbon-ion beams significantly reduced crawling motility at 3 kGy. Next, swimming in buffer was measured as a motility index to assess the response over time after irradiation and motility similarly decreased. However, swimming partially recovered 6 h after irradiation with 3 kGy of γ-rays. To examine the possibility of a recovery mechanism, in situ GFP reporter assay of the autophagy-related gene lgg-1 was performed. The fluorescence intensity was stronger in the anterior half of the body 7 h after irradiation with 3 kGy of γ-rays. GFP::LGG-1 induction was observed in the pharynx, neurons along the body, and the intestine. Furthermore, worms were exposed to region-specific radiation with carbon-ion microbeams and the trajectory of crawling was measured by image processing. Motility was lower after anterior-half body irradiation than after posterior-half body irradiation. This further supported that the anterior half of the body is important in the locomotory response to radiation. Full article
(This article belongs to the Special Issue Molecular Research in Radiobiology)
►▼ Show Figures

Figure 1

13 pages, 1209 KiB  
Article
Analysis of the Applicability of microRNAs in Peripheral Blood Leukocytes as Biomarkers of Sensitivity and Exposure to Fractionated Radiotherapy towards Breast Cancer
by Michal Marczyk, Joanna Polańska, Andrzej Wojcik and Lovisa Lundholm
Int. J. Mol. Sci. 2021, 22(16), 8705; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168705 - 13 Aug 2021
Cited by 3 | Viewed by 1862
Abstract
Biomarkers for predicting individual response to radiation and for dose verification are needed to improve radiotherapy. A biomarker should optimally show signal fidelity, meaning that its level is stable and proportional to the absorbed dose. miRNA levels in human blood serum were suggested [...] Read more.
Biomarkers for predicting individual response to radiation and for dose verification are needed to improve radiotherapy. A biomarker should optimally show signal fidelity, meaning that its level is stable and proportional to the absorbed dose. miRNA levels in human blood serum were suggested as promising biomarkers. The aim of the present investigation was to test the miRNA biomarker in leukocytes of breast cancer patients undergoing external beam radiotherapy. Leukocytes were isolated from blood samples collected prior to exposure (control); on the day when a total dose of 2 Gy, 10 Gy, or 20 Gy was reached; and one month after therapy ended (46–50 Gy in total). RNA sequencing was performed and univariate analysis was used to analyse the effect of the radiation dose on the expression of single miRNAs. To check if combinations of miRNAs can predict absorbed dose, a multinomial logistic regression model was built using a training set from eight patients (representing 40 samples) and a validation set with samples from the remaining eight patients (15 samples). Finally, Broadside, an explorative interaction mining tool, was used to extract sets of interacting miRNAs. The most prominently increased miRNA was miR-744-5p, followed by miR-4461, miR-34a-5p, miR-6513-5p, miR-1246, and miR-454-3p. Decreased miRNAs were miR-3065-3p, miR-103a-2-5p, miR-30b-3p, and miR-5690. Generally, most miRNAs showed a relatively strong inter-individual variability and different temporal patterns over the course of radiotherapy. In conclusion, miR-744-5p shows promise as a stable miRNA marker, but most tested miRNAs displayed individual signal variability which, at least in this setting, may exclude them as sensitive biomarkers of radiation response. Full article
(This article belongs to the Special Issue Molecular Research in Radiobiology)
►▼ Show Figures

Figure 1

17 pages, 3024 KiB  
Article
Coralyne Radiosensitizes A549 Cells by Upregulation of CDKN1A Expression to Attenuate Radiation Induced G2/M Block of the Cell Cycle
by Aneta Węgierek-Ciuk, Michał Arabski, Karol Ciepluch, Kamil Brzóska, Halina Lisowska, Malwina Czerwińska, Tomasz Stępkowski, Krzysztof Lis and Anna Lankoff
Int. J. Mol. Sci. 2021, 22(11), 5791; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115791 - 28 May 2021
Cited by 4 | Viewed by 2449
Abstract
Coralyne is a synthetic analog of berberine related to protoberberine-isoquinoline alkaloids. Isoquinoline derivatives and analogs are renowned as potent radiosensitizers with potential medical application. In the present study, we investigated the effect of coralyne on the cell death, cytoskeletal changes and cell cycle [...] Read more.
Coralyne is a synthetic analog of berberine related to protoberberine-isoquinoline alkaloids. Isoquinoline derivatives and analogs are renowned as potent radiosensitizers with potential medical application. In the present study, we investigated the effect of coralyne on the cell death, cytoskeletal changes and cell cycle progression of irradiated A549 cells. A clonogenic assay revealed that coralyne pretreatment decreased the viability of A549 cells in a time- and dose-dependent manner. Moreover, exposure to coralyne and ionizing radiation (IR) markedly altered the filamentous actin cytoskeletal architecture and integrin-β binding sites of A549 cells. Treatment with 1–25 µM coralyne in combination with 2 Gy of IR significantly reduced the percentage of cells in G2/M phase compared with 2 Gy IR alone. These results indicate that coralyne is a potent radiosensitizing agent that may find an application in medicine. Full article
(This article belongs to the Special Issue Molecular Research in Radiobiology)
►▼ Show Figures

Figure 1

29 pages, 5783 KiB  
Article
Out-of-Field Hippocampus from Partial-Body Irradiated Mice Displays Changes in Multi-Omics Profile and Defects in Neurogenesis
by Simonetta Pazzaglia, Barbara Tanno, Francesca Antonelli, Paola Giardullo, Gabriele Babini, Prabal Subedi, Omid Azimzadeh, Zohaib N. Khan, Kateryna Oleksenko, Fabian Metzger, Christine von Toerne, Damien Traynor, Dinesh Medipally, Aidan D. Meade, Munira Kadhim, Fiona M. Lyng, Soile Tapio, Anna Saran and Mariateresa Mancuso
Int. J. Mol. Sci. 2021, 22(8), 4290; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084290 - 20 Apr 2021
Cited by 5 | Viewed by 3703
Abstract
The brain undergoes ionizing radiation exposure in many clinical situations, particularly during radiotherapy for brain tumors. The critical role of the hippocampus in the pathogenesis of radiation-induced neurocognitive dysfunction is well recognized. The goal of this study is to test the potential contribution [...] Read more.
The brain undergoes ionizing radiation exposure in many clinical situations, particularly during radiotherapy for brain tumors. The critical role of the hippocampus in the pathogenesis of radiation-induced neurocognitive dysfunction is well recognized. The goal of this study is to test the potential contribution of non-targeted effects in the detrimental response of the hippocampus to irradiation and to elucidate the mechanisms involved. C57Bl/6 mice were whole body (WBI) or partial body (PBI) irradiated with 0.1 or 2.0 Gy of X-rays or sham irradiated. PBI consisted of the exposure of the lower third of the mouse body, whilst the upper two thirds were shielded. Hippocampi were collected 15 days or 6 months post-irradiation and a multi-omics approach was adopted to assess the molecular changes in non-coding RNAs, proteins and metabolic levels, as well as histological changes in the rate of hippocampal neurogenesis. Notably, at 2.0 Gy the pattern of early molecular and histopathological changes induced in the hippocampus at 15 days following PBI were similar in quality and quantity to the effects induced by WBI, thus providing a proof of principle of the existence of out-of-target radiation response in the hippocampus of conventional mice. We detected major alterations in DAG/IP3 and TGF-β signaling pathways as well as in the expression of proteins involved in the regulation of long-term neuronal synaptic plasticity and synapse organization, coupled with defects in neural stem cells self-renewal in the hippocampal dentate gyrus. However, compared to the persistence of the WBI effects, most of the PBI effects were only transient and tended to decrease at 6 months post-irradiation, indicating important mechanistic difference. On the contrary, at low dose we identified a progressive accumulation of molecular defects that tended to manifest at later post-irradiation times. These data, indicating that both targeted and non-targeted radiation effects might contribute to the pathogenesis of hippocampal radiation-damage, have general implications for human health. Full article
(This article belongs to the Special Issue Molecular Research in Radiobiology)
►▼ Show Figures

Figure 1

Review

Jump to: Research

22 pages, 826 KiB  
Review
Commonalities in the Features of Cancer and Chronic Fatigue Syndrome (CFS): Evidence for Stress-Induced Phenotype Instability?
by Andrej Rusin, Colin Seymour, Alan Cocchetto and Carmel Mothersill
Int. J. Mol. Sci. 2022, 23(2), 691; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23020691 - 08 Jan 2022
Cited by 12 | Viewed by 4206
Abstract
Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) and Cancer-Related Fatigue (CRF) are syndromes with considerable overlap with respect to symptoms. There have been many studies that have compared the two conditions, and some of this research suggests that the etiologies of the conditions are linked [...] Read more.
Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) and Cancer-Related Fatigue (CRF) are syndromes with considerable overlap with respect to symptoms. There have been many studies that have compared the two conditions, and some of this research suggests that the etiologies of the conditions are linked in some cases. In this narrative review, CFS/ME and cancer are introduced, along with their known and putative mechanistic connections to multiple stressors including ionizing radiation. Next, we summarize findings from the literature that suggest the involvement of HPA-axis dysfunction, the serotonergic system, cytokines and inflammation, metabolic insufficiency and mitochondrial dysfunction, and genetic changes in CRF and CFS/ME. We further suspect that the manifestation of fatigue in both diseases and its causes could indicate that CRF and CFS/ME lie on a continuum of potential biological effects which occur in response to stress. The response to this stress likely varies depending on predisposing factors such as genetic background. Finally, future research ideas are suggested with a focus on determining if common biomarkers exist in CFS/ME patients and those afflicted with CRF. Both CFS/ME and CRF are relatively heterogenous syndromes, however, it is our hope that this review assists in future research attempting to elucidate the commonalities between CRF and CFS/ME. Full article
(This article belongs to the Special Issue Molecular Research in Radiobiology)
►▼ Show Figures

Figure 1

30 pages, 28536 KiB  
Review
Targeted and Non-Targeted Mechanisms for Killing Hypoxic Tumour Cells—Are There New Avenues for Treatment?
by Alyssa Gabrielle Apilan and Carmel Mothersill
Int. J. Mol. Sci. 2021, 22(16), 8651; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168651 - 11 Aug 2021
Cited by 2 | Viewed by 3167
Abstract
Purpose: A major issue in radiotherapy is the relative resistance of hypoxic cells to radiation. Historic approaches to this problem include the use of oxygen mimetic compounds to sensitize tumour cells, which were unsuccessful. This review looks at modern approaches aimed at increasing [...] Read more.
Purpose: A major issue in radiotherapy is the relative resistance of hypoxic cells to radiation. Historic approaches to this problem include the use of oxygen mimetic compounds to sensitize tumour cells, which were unsuccessful. This review looks at modern approaches aimed at increasing the efficacy of targeting and radiosensitizing hypoxic tumour microenvironments relative to normal tissues and asks the question of whether non-targeted effects in radiobiology may provide a new “target”. Novel techniques involve the integration of recent technological advancements such as nanotechnology, cell manipulation, and medical imaging. Particularly, the major areas of research discussed in this review include tumour hypoxia imaging through PET imaging to guide carbogen breathing, gold nanoparticles, macrophage-mediated drug delivery systems used for hypoxia-activate prodrugs, and autophagy inhibitors. Furthermore, this review outlines several features of these methods, including the mechanisms of action to induce radiosensitization, the increased accuracy in targeting hypoxic tumour microenvironments relative to normal tissue, preclinical/clinical trials, and future considerations. Conclusions: This review suggests that the four novel tumour hypoxia therapeutics demonstrate compelling evidence that these techniques can serve as powerful tools to increase targeting efficacy and radiosensitizing hypoxic tumour microenvironments relative to normal tissue. Each technique uses a different way to manipulate the therapeutic ratio, which we have labelled “oxygenate, target, use, and digest”. In addition, by focusing on emerging non-targeted and out-of-field effects, new umbrella targets are identified, which instead of sensitizing hypoxic cells, seek to reduce the radiosensitivity of normal tissues. Full article
(This article belongs to the Special Issue Molecular Research in Radiobiology)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-16
Back to TopTop