Biomedicines

Editorial

Jump to: Research, Review

3 pages, 200 KiB

Open AccessEditorial

New Insights in Radiotherapy

by Carlos Martínez-Campa

Biomedicines 2022, 10(8), 1931; https://doi.org/10.3390/biomedicines10081931 - 09 Aug 2022

Viewed by 1264

Abstract

This Special Issue of Biomedicines, entitled “New insights in Radiotherapy”, compiles insightful reviews on the state of the art on different aspects of radiation therapy, and also collects high-quality research articles highlighting the latest advances in the use of ionizing radiation to [...] Read more.

This Special Issue of Biomedicines, entitled “New insights in Radiotherapy”, compiles insightful reviews on the state of the art on different aspects of radiation therapy, and also collects high-quality research articles highlighting the latest advances in the use of ionizing radiation to treat a variety of specific diseases, including cancer, either with curative of palliative purposes [...] Full article

(This article belongs to the Special Issue New Insights in Radiotherapy)

Research

Jump to: Editorial, Review

21 pages, 3015 KiB

Open AccessArticle

Melatonin Modulation of Radiation-Induced Molecular Changes in MCF-7 Human Breast Cancer Cells

by Carolina Alonso-González, Cristina González-Abalde, Javier Menéndez-Menéndez, Alicia González-González, Virginia Álvarez-García, Alicia González-Cabeza, Carlos Martínez-Campa and Samuel Cos

Biomedicines 2022, 10(5), 1088; https://doi.org/10.3390/biomedicines10051088 - 07 May 2022

Cited by 4 | Viewed by 2374

Abstract

Radiation therapy is an important component of cancer treatment scheduled for cancer patients, although it can cause numerous deleterious effects. The use of adjuvant molecules aims to limit the damage in normal surrounding tissues and enhance the effects of radiation therapy, either killing [...] Read more.

Radiation therapy is an important component of cancer treatment scheduled for cancer patients, although it can cause numerous deleterious effects. The use of adjuvant molecules aims to limit the damage in normal surrounding tissues and enhance the effects of radiation therapy, either killing tumor cells or slowing down their growth. Melatonin, an indoleamine released by the pineal gland, behaves as a radiosensitizer in breast cancer, since it enhances the therapeutic effects of ionizing radiation and mitigates side effects on normal cells. However, the molecular mechanisms through which melatonin modulates the molecular changes triggered by radiotherapy remain mostly unknown. Here, we report that melatonin potentiated the anti-proliferative effect of radiation in MCF-7 cells. Treatment with ionizing radiation induced changes in the expression of many genes. Out of a total of 25 genes altered by radiation, melatonin potentiated changes in 13 of them, whereas the effect was reverted in another 10 cases. Among them, melatonin elevated the levels of PTEN and NME1, and decreased the levels of SNAI2, ERBB2, AKT, SERPINE1, SFN, PLAU, ATM and N3RC1. We also analyzed the expression of several microRNAs and found that melatonin enhanced the effect of radiation on the levels of miR-20a, miR-19a, miR-93, miR-20b and miR-29a. Rather surprisingly, radiation induced miR-17, miR-141 and miR-15a but melatonin treatment prior to radiation counteracted this stimulatory effect. Radiation alone enhanced the expression of the cancer suppressor miR-34a, and melatonin strongly stimulated this effect. Melatonin further enhanced the radiation-mediated inhibition of Akt. Finally, in an in vivo assay, melatonin restrained new vascularization in combination with ionizing radiation. Our results confirm that melatonin blocks many of the undesirable effects of ionizing radiation in MCF-7 cells and enhances changes that lead to optimized treatment results. This article highlights the effectiveness of melatonin as both a radiosensitizer and a radioprotector in breast cancer. Melatonin is an effective adjuvant molecule to radiotherapy, promoting anti-cancer therapeutic effects in cancer treatment. Melatonin modulates molecular pathways altered by radiation, and its use in clinic might lead to improved therapeutic outcomes by enhancing the sensitivity of cancerous cells to radiation and, in general, reversing their resistance toward currently applied therapeutic modalities. Full article

(This article belongs to the Special Issue New Insights in Radiotherapy)

► Show Figures

Figure 1

12 pages, 4682 KiB

Open AccessArticle

Dendrobine Inhibits γ-Irradiation-Induced Cancer Cell Migration, Invasion and Metastasis in Non-Small Cell Lung Cancer Cells

by Ye-Ram Kim, Ah-Reum Han, Jin-Baek Kim and Chan-Hun Jung

Biomedicines 2021, 9(8), 954; https://doi.org/10.3390/biomedicines9080954 - 03 Aug 2021

Cited by 8 | Viewed by 2296

Abstract

The use of ionizing radiation (IR) during radiotherapy can induce malignant effects, such as metastasis, which contribute to poor prognoses in lung cancer patients. Here, we explored the ability of dendrobine, a plant-derived alkaloid from Dendrobium nobile, to improve the efficacy of [...] Read more.

The use of ionizing radiation (IR) during radiotherapy can induce malignant effects, such as metastasis, which contribute to poor prognoses in lung cancer patients. Here, we explored the ability of dendrobine, a plant-derived alkaloid from Dendrobium nobile, to improve the efficacy of radiotherapy in non-small cell lung cancer (NSCLC). We employed Western blotting, quantitative real-time (qRT)-PCR, transwell migration assays, and wound-healing assays to determine the effects of dendrobine on the migration and invasion of A549 lung cancer cells in vitro. Dendrobine (5 mm) inhibited γ-irradiation-induced migration and invasion of A549 cells by suppressing sulfatase2 (SULF2) expression, thus inhibiting IR-induced signaling. To investigate the inhibitory effects of dendrobine in vivo, we established a mouse model of IR-induced metastasis by injecting BALB/c nude mice with γ-irradiated A549 cells via the tail vein. As expected, injection with γ-irradiated cells increased the number of pulmonary metastatic nodules in mice (0 Gy/DPBS, 9.8 ± 1.77; 2 Gy/DPBS, 20.87 ± 1.42), which was significantly reduced with dendrobine treatment (2 Gy/Dendrobine, 10.87 ± 0.71), by prevention of IR-induced signaling. Together, these findings demonstrate that dendrobine exerts inhibitory effects against γ-irradiation-induced invasion and metastasis in NSCLC cells in vitro and in vivo at non cytotoxic concentrations. Thus, dendrobine could serve as a therapeutic enhancer to overcome the malignant effects of radiation therapy in patients with NSCLC. Full article

(This article belongs to the Special Issue New Insights in Radiotherapy)

► Show Figures

Figure 1

19 pages, 3151 KiB

Open AccessArticle

Radiotherapy in Follicular Lymphoma Staged by ¹⁸F-FDG-PET/CT: A German Monocenter Study

by Imke E. Karsten, Gabriele Reinartz, Michaela Pixberg, Kai Kröger, Michael Oertel, Birte Friedrichs, Georg Lenz and Hans Theodor Eich

Biomedicines 2021, 9(5), 561; https://doi.org/10.3390/biomedicines9050561 - 17 May 2021

Cited by 4 | Viewed by 3577

Abstract

This retrospective study examined the role of ¹⁸F-fluorodeoxyglucose-positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) in stage-related therapy of follicular lymphomas (FL). Twelve patients each in stages I and II, 13 in stage III and 11 in stage IV were treated in the [...] Read more.

This retrospective study examined the role of ¹⁸F-fluorodeoxyglucose-positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) in stage-related therapy of follicular lymphomas (FL). Twelve patients each in stages I and II, 13 in stage III and 11 in stage IV were treated in the Department of Radiation Oncology, University Hospital of Muenster, Germany from 2004 to 2016. Radiotherapy (RT), as well as additional chemoimmunotherapy were analyzed with a median follow-up of 87.6 months. Ultrasound (US), CT and ¹⁸F-FDG-PET/CT were used to determine progression-free survival (PFS), overall survival (OS) and lymphoma-specific survival (LSS) over 5- and 10- years. 23 of 24 patients with stage I/II (95.8%) had complete remissions (CR) and 17 of 24 patients with stages III/IV FL showed CR (70.8%). 5- and 10-year PFS in stages I/II was 90.0%/78.1% vs. 44.3%/28.5% in stages III/IV. 5- and 10-year OS rates in stages I/II was 100%/93.3% vs. 53.7%/48.4% in stages III/IV. 5- and 10-year LSS of stages I/II was 100%/93.8% vs. 69.2%/62.3% in stages III/IV. FL of stages I/II, staged by ¹⁸F-FDG-PET/CT, revealed better survival rates and lower risk of recurrence compared to studies without PET/CT-staging. Especially, patients with PET/CT proven stage I disease showed significantly better survival and lower relapses rates after RT. Full article

(This article belongs to the Special Issue New Insights in Radiotherapy)

► Show Figures

Figure 1

24 pages, 8206 KiB

Open AccessArticle

Oxygen-Carrying Polymer Nanoconstructs for Radiodynamic Therapy of Deep Hypoxic Malignant Tumors

by Sandhya Clement, Anna Guller, Saabah B. Mahbub and Ewa M. Goldys

Biomedicines 2021, 9(3), 322; https://doi.org/10.3390/biomedicines9030322 - 22 Mar 2021

Cited by 12 | Viewed by 3416

Abstract

Radiodynamic therapy (RDT) is an emerging non-invasive anti-cancer treatment based on the generation of the reactive oxygen species (ROS) at the lesion site following the interaction between X-rays and a photosensitizer drug (PS). The broader application of RDT is impeded by the tumor-associated [...] Read more.

Radiodynamic therapy (RDT) is an emerging non-invasive anti-cancer treatment based on the generation of the reactive oxygen species (ROS) at the lesion site following the interaction between X-rays and a photosensitizer drug (PS). The broader application of RDT is impeded by the tumor-associated hypoxia that results in low availability of oxygen for the generation of sufficient amounts of ROS. Herein, a novel nanoparticle drug formulation for RDT, which addresses the problem of low oxygen availability, is reported. It consists of poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) co-loaded with a PS drug verteporfin (VP), and the clinically approved oxygen-carrying molecule, perfluorooctylbromide (PFOB). When triggered by X-rays (4 Gy), under both normoxic and hypoxic conditions, PLGA–VP–PFOB nanoconstructs (NCs) induced a significant increase of the ROS production compared with matching PLGA–VP nanoparticles. The RDT with NCs effectively killed ~60% of human pancreatic cancer cells in monolayer cultures, and almost completely suppressed the outgrowth of tumor cells in 2-weeks clonogenic assay. In a 3D engineered model of pancreatic cancer metastasis to the liver, RDT with NCs destroyed ~35% of tumor cells, demonstrating an exceptional efficiency at a tissue level. These results show that PLGA–VP–PFOB is a promising agent for RDT of deep-seated hypoxic tumors. Full article

(This article belongs to the Special Issue New Insights in Radiotherapy)

► Show Figures

Figure 1

13 pages, 477 KiB

Open AccessArticle

Reinforcement Learning for Radiotherapy Dose Fractioning Automation

by Grégoire Moreau, Vincent François-Lavet, Paul Desbordes and Benoît Macq

Biomedicines 2021, 9(2), 214; https://doi.org/10.3390/biomedicines9020214 - 19 Feb 2021

Cited by 9 | Viewed by 3233

Abstract

External beam radiotherapy cancer treatment aims to deliver dose fractions to slowly destroy a tumor while avoiding severe side effects in surrounding healthy tissues. To automate the dose fraction schedules, this paper investigates how deep reinforcement learning approaches (based on deep Q network [...] Read more.

External beam radiotherapy cancer treatment aims to deliver dose fractions to slowly destroy a tumor while avoiding severe side effects in surrounding healthy tissues. To automate the dose fraction schedules, this paper investigates how deep reinforcement learning approaches (based on deep Q network and deep deterministic policy gradient) can learn from a model of a mixture of tumor and healthy cells. A 2D tumor growth simulation is used to simulate radiation effects on tissues and thus training an agent to automatically optimize dose fractionation. Results show that initiating treatment with large dose per fraction, and then gradually reducing it, is preferred to the standard approach of using a constant dose per fraction. Full article

(This article belongs to the Special Issue New Insights in Radiotherapy)

► Show Figures

Figure 1

15 pages, 4413 KiB

Open AccessArticle

Combinatorial Effect of Magnetic Field and Radiotherapy in PDAC Organoids: A Pilot Study

by Luca Nicosia, Filippo Alongi, Silvia Andreani, Ruggero Ruggieri, Borislav Rusev, Beatrice Mantoan, Rita Teresa Lawlor, Antonio Pea, Aldo Scarpa, Linda Agolli, Vincenzo Corbo and Sabrina D’Agosto

Biomedicines 2020, 8(12), 609; https://doi.org/10.3390/biomedicines8120609 - 14 Dec 2020

Cited by 7 | Viewed by 2433

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is highly refractory to systemic treatment, including radiotherapy (RT) either as alone or in combination with chemotherapy. Magnetic resonance (MR)-guided RT is a novel treatment technique which conjugates the high MR imaging contrast resolution to the possibility of re-adapting [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is highly refractory to systemic treatment, including radiotherapy (RT) either as alone or in combination with chemotherapy. Magnetic resonance (MR)-guided RT is a novel treatment technique which conjugates the high MR imaging contrast resolution to the possibility of re-adapting treatment plan to daily anatomical variations. Magnetic field (MF) might exert a biological effect that could be exploited to enhance radiation effect. The aim of the present study was to lay the preclinical basis of the MF effect by exploring how it modifies the response to radiation in organoid cultures established from PDAC. The short-term effect of radiation, alone or in combination with MF, was evaluated in patient-derived organoids (PDOs) and monolayer cell cultures. Cell viability, apoptotic cell death, and organoid size following exposure to the treatment were evaluated. PDOs demonstrated limited sensitivity at clinically relevant doses of radiation. The combination of radiation and MF demonstrated superior efficacy than monotherapy in almost all the PDOs tested. PDOs treated with combination of radiation and MF were significantly smaller in size and some showed increased cell death as compared to the monotherapy with radiation. Long-time exposure to 1.5T MF can increase the therapeutic efficacy of radiation in PDAC organoids. Full article

(This article belongs to the Special Issue New Insights in Radiotherapy)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

20 pages, 902 KiB

Open AccessReview

Cytoskeleton Response to Ionizing Radiation: A Brief Review on Adhesion and Migration Effects

by Giuseppe La Verde, Valeria Artiola, Valeria Panzetta, Mariagabriella Pugliese, Paolo A. Netti and Sabato Fusco

Biomedicines 2021, 9(9), 1102; https://doi.org/10.3390/biomedicines9091102 - 28 Aug 2021

Cited by 9 | Viewed by 3124

Abstract

The cytoskeleton is involved in several biological processes, including adhesion, motility, and intracellular transport. Alterations in the cytoskeletal components (actin filaments, intermediate filaments, and microtubules) are strictly correlated to several diseases, such as cancer. Furthermore, alterations in the cytoskeletal structure can lead to [...] Read more.

The cytoskeleton is involved in several biological processes, including adhesion, motility, and intracellular transport. Alterations in the cytoskeletal components (actin filaments, intermediate filaments, and microtubules) are strictly correlated to several diseases, such as cancer. Furthermore, alterations in the cytoskeletal structure can lead to anomalies in cells’ properties and increase their invasiveness. This review aims to analyse several studies which have examined the alteration of the cell cytoskeleton induced by ionizing radiations. In particular, the radiation effects on the actin cytoskeleton, cell adhesion, and migration have been considered to gain a deeper knowledge of the biophysical properties of the cell. In fact, the results found in the analysed works can not only aid in developing new diagnostic tools but also improve the current cancer treatments. Full article

(This article belongs to the Special Issue New Insights in Radiotherapy)

► Show Figures

Figure 1

57 pages, 719 KiB

Open AccessReview

Radioprotection and Radiomitigation: From the Bench to Clinical Practice

by Elena Obrador, Rosario Salvador, Juan I. Villaescusa, José M. Soriano, José M. Estrela and Alegría Montoro

Biomedicines 2020, 8(11), 461; https://doi.org/10.3390/biomedicines8110461 - 30 Oct 2020

Cited by 72 | Viewed by 9574

Abstract

The development of protective agents against harmful radiations has been a subject of investigation for decades. However, effective (ideal) radioprotectors and radiomitigators remain an unsolved problem. Because ionizing radiation-induced cellular damage is primarily attributed to free radicals, radical scavengers are promising as potential [...] Read more.

The development of protective agents against harmful radiations has been a subject of investigation for decades. However, effective (ideal) radioprotectors and radiomitigators remain an unsolved problem. Because ionizing radiation-induced cellular damage is primarily attributed to free radicals, radical scavengers are promising as potential radioprotectors. Early development of such agents focused on thiol synthetic compounds, e.g., amifostine (2-(3-aminopropylamino) ethylsulfanylphosphonic acid), approved as a radioprotector by the Food and Drug Administration (FDA, USA) but for limited clinical indications and not for nonclinical uses. To date, no new chemical entity has been approved by the FDA as a radiation countermeasure for acute radiation syndrome (ARS). All FDA-approved radiation countermeasures (filgrastim, a recombinant DNA form of the naturally occurring granulocyte colony-stimulating factor, G-CSF; pegfilgrastim, a PEGylated form of the recombinant human G-CSF; sargramostim, a recombinant granulocyte macrophage colony-stimulating factor, GM-CSF) are classified as radiomitigators. No radioprotector that can be administered prior to exposure has been approved for ARS. This differentiates radioprotectors (reduce direct damage caused by radiation) and radiomitigators (minimize toxicity even after radiation has been delivered). Molecules under development with the aim of reaching clinical practice and other nonclinical applications are discussed. Assays to evaluate the biological effects of ionizing radiations are also analyzed. Full article

(This article belongs to the Special Issue New Insights in Radiotherapy)

► Show Figures

Figure 1

24 pages, 771 KiB

Open AccessReview

Positron Emission Tomography for Response Evaluation in Microenvironment-Targeted Anti-Cancer Therapy

by Noboru Oriuchi, Shigeyasu Sugawara and Tohru Shiga

Biomedicines 2020, 8(9), 371; https://doi.org/10.3390/biomedicines8090371 - 22 Sep 2020

Cited by 11 | Viewed by 3819

Abstract

Therapeutic response is evaluated using the diameter of tumors and quantitative parameters of 2-[¹⁸F] fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET). Tumor response to molecular-targeted drugs and immune checkpoint inhibitors is different from conventional chemotherapy in terms of temporal metabolic alteration [...] Read more.

Therapeutic response is evaluated using the diameter of tumors and quantitative parameters of 2-[¹⁸F] fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET). Tumor response to molecular-targeted drugs and immune checkpoint inhibitors is different from conventional chemotherapy in terms of temporal metabolic alteration and morphological change after the therapy. Cancer stem cells, immunologically competent cells, and metabolism of cancer are considered targets of novel therapy. Accumulation of FDG reflects the glucose metabolism of cancer cells as well as immune cells in the tumor microenvironment, which differs among patients according to the individual immune function; however, FDG-PET could evaluate the viability of the tumor as a whole. On the other hand, specific imaging and cell tracking of cancer cell or immunological cell subsets does not elucidate tumor response in a complexed interaction in the tumor microenvironment. Considering tumor heterogeneity and individual variation in therapeutic response, a radiomics approach with quantitative features of multimodal images and deep learning algorithm with reference to pathologic and genetic data has the potential to improve response assessment for emerging cancer therapy. Full article

(This article belongs to the Special Issue New Insights in Radiotherapy)

► Show Figures

Figure 1

20 pages, 1719 KiB

Open AccessReview

Melatonin as a Radio-Sensitizer in Cancer

by Carolina Alonso-González, Alicia González, Javier Menéndez-Menéndez, Carlos Martínez-Campa and Samuel Cos

Biomedicines 2020, 8(8), 247; https://doi.org/10.3390/biomedicines8080247 - 27 Jul 2020

Cited by 16 | Viewed by 3724

Abstract

Radiotherapy is one of the treatments of choice in many types of cancer. Adjuvant treatments to radiotherapy try, on one hand, to enhance the response of tumor cells to radiation and, on the other hand, to reduce the side effects to normal cells. [...] Read more.

Radiotherapy is one of the treatments of choice in many types of cancer. Adjuvant treatments to radiotherapy try, on one hand, to enhance the response of tumor cells to radiation and, on the other hand, to reduce the side effects to normal cells. Radiosensitizers are agents that increase the effect of radiation in tumor cells by trying not to increase side effects in normal tissues. Melatonin is a hormone produced mainly by the pineal gland which has an important role in the regulation of cancer growth, especially in hormone-dependent mammary tumors. Different studies have showed that melatonin administered with radiotherapy is able to enhance its therapeutic effects and can protect normal cells against side effects of this treatment. Several mechanisms are involved in the radiosensitization induced by melatonin: increase of reactive oxygen species production, modulation of proteins involved in estrogen biosynthesis, impairment of tumor cells to DNA repair, modulation of angiogenesis, abolition of inflammation, induction of apoptosis, stimulation of preadipocytes differentiation and modulation of metabolism. At this moment, there are very few clinical trials that study the therapeutic usefulness to associate melatonin and radiotherapy in humans. All findings point to melatonin as an effective adjuvant molecule to radiotherapy in cancer treatment. Full article

(This article belongs to the Special Issue New Insights in Radiotherapy)

► Show Figures

Figure 1

Journal Menu

Journal Browser

New Insights in Radiotherapy

Share This Special Issue

Special Issue Editor

Special Issue Information

Published Papers (11 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI