scholarly journals Predictors of radiation-induced complications in radiation oncology based on cell survival tests after ex vivo exposure: literature review

2021 ◽  
Vol 29 (1) ◽  
pp. 89-118
Author(s):  
V. A. Vinnikov ◽  
T. V. Rubleva
Keyword(s):  
Cell Death ◽  
Cell Survival ◽  
Radiation Oncology ◽  
Radiation Effects ◽  
Ex Vivo ◽  
Radiation Toxicity ◽  
Normal Tissues ◽  
Intrinsic Radiosensitivity ◽  
Radiation Induced ◽  
Clonogenic Cell

Background. Among cancer patients receiving radiotherapy about 5–15 % may have adverse reactions in normal tissues and organs that limit their treatment in a full, originally scheduled regimen. The development of biomarkers and assays for radiation oncology allowing the prediction of patients’ normal tissue toxicity requires a lot of resourses, threfore its current status amd potential directions for future research have to be periodically analyzed and re-evaluated. Purpose – this review summarizes the methodological approaches and developments in the area of functional laboratory assays based on ex vivo cell survival for the prediction of the individual clinical radiosensitivity. Materials and methods. Data for the analysis and systematization were obtained from the full-text articles published in peer review international scientific journals (in English) in 1990–2020, which were selected by the extensive search in PubMed information database and cross references on the topic “Functional cellular tests for intrinsic radiosensitivity to predict adverse radiation effects and radiotherapy complications”. Results. In theory, it might be expected that clonogenic cell survival after ex vivo irradiation can surve as the best individual predictor of radiation toxicity, as it is an integral indicator of cell damage and decline of their regenerative potential. Tendentially, fibroblasts, as a test system for such studies, did not show significant advantages over lymphocytes either in detecting inter-individual variations in the intrinsic cellular radiosensitivity or in predicting clinical radiation toxicity, even for that in skin. It was found that clonogenic cell survival assay, being very time consuming and technically demanding, also suffers from the lack of sensitivity and specificity, essential uncertainty and low reproducibility of the results, and thus is not suitable for the sceening for the abnormal intrinsic radiosensitivity. However, this type of assays is applicable for the radiobiological expertise post factum in individual cases with unexpected, extreme radiation lesions. Radiation-induced lymphocyte apoptosis assay seems to be more promising however still requires further fundamental research for better understanding of its background and more validation studies in order to assess the optimum patient groups, radiotherapy regimens and adverse effects for its confident use in clinical practice. Changes in the regulation of cell cycle check-points (radiationinduced delay) ex vivo can have either positive or inverted association, or no correlation with clinical radiation responses in tissues, thus so far cannot be included in the toolbox of applied radiobiological tests. Conclusions. To date, in the practice of clinical radiobiology, there are no fully validated and standardized functional tests based on the cell survival after ex vivo irradiation, which would allow a sufficiently accurate prediction of adverse radiation effects in normal tissues of radiotherapy patients. In general, ex vivo tests based on the evaluation of only one form of cell death in one cell type are not fully reliable as a “stand alone” assay, because different pathways of cell death probably play different roles and show different dose response within the overal reaction of the irradiated tissue or critical organ. Such tests should become a part of the multiparametric predictive platforms.

scholarly journals Protective Effects of p53 Regulatory Agents Against High-LET Radiation-Induced Injury in Mice

2020 ◽  
Vol 8 ◽  
Author(s):  
Akinori Morita ◽  
Bing Wang ◽  
Kaoru Tanaka ◽  
Takanori Katsube ◽  
Masahiro Murakami ◽  
...  
Keyword(s):  
Cell Death ◽  
Radiation Injury ◽  
Ion Irradiation ◽  
Heavy Ion ◽  
Protective Effects ◽  
Iron Ion ◽  
Normal Tissues ◽  
High Let Radiation ◽  
High Let ◽  
Radiation Induced

Radiation damage to normal tissues is one of the most serious concerns in radiation therapy, and the tolerance dose of the normal tissues limits the therapeutic dose to the patients. p53 is well known as a transcription factor closely associated with radiation-induced cell death. We recently demonstrated the protective effects of several p53 regulatory agents against low-LET X- or γ-ray-induced damage. Although it was reported that high-LET heavy ion radiation (>85 keV/μm) could cause p53-independent cell death in some cancer cell lines, whether there is any radioprotective effect of the p53 regulatory agents against the high-LET radiation injury in vivo is still unclear. In the present study, we verified the efficacy of these agents on bone marrow and intestinal damages induced by high-LET heavy-ion irradiation in mice. We used a carbon-beam (14 keV/μm) that was shown to induce a p53-dependent effect and an iron-beam (189 keV/μm) that was shown to induce a p53-independent effect in a previous study. Vanadate significantly improved 60-day survival rate in mice treated with total-body carbon-ion (p < 0.0001) or iron-ion (p < 0.05) irradiation, indicating its effective protection of the hematopoietic system from radiation injury after high-LET irradiation over 85 keV/μm. 5CHQ also significantly increased the survival rate after abdominal carbon-ion (p < 0.02), but not iron-ion irradiation, suggesting the moderate relief of the intestinal damage. These results demonstrated the effectiveness of p53 regulators on acute radiation syndrome induced by high-LET radiation.

Gangliosides protect human melanoma cells from ionizing radiation-induced clonogenic cell death

1996 ◽  
Vol 13 (3) ◽  
pp. 377-384 ◽  
Author(s):  
C. P. Thomas ◽  
A. Buronfosse ◽  
V. Combaret ◽  
S. Pedron ◽  
B. Fertil ◽  
...  
Keyword(s):  
Cell Death ◽  
Ionizing Radiation ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Human Melanoma Cells ◽  
Radiation Induced ◽  
Clonogenic Cell

scholarly journals Bovine Leukemia Virus-Induced Persistent Lymphocytosis in Cattle Does Not Correlate with Increased Ex Vivo Survival of B Lymphocytes

1999 ◽  
Vol 73 (2) ◽  
pp. 1127-1137 ◽  
Author(s):  
Franck Dequiedt ◽  
Glenn H. Cantor ◽  
Valerie T. Hamilton ◽  
Suzanne M. Pritchard ◽  
William C. Davis ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Survival ◽  
Bovine Leukemia Virus ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Leukemia Virus ◽  
Spontaneous Apoptosis ◽  
Persistent Lymphocytosis ◽  
Peripheral Blood Mononuclear

ABSTRACT Bovine leukemia virus (BLV) is an oncogenic retrovirus associated with B-cell lymphocytosis, leukemia, and lymphosarcoma in the ovine and bovine species. We have recently reported that in sheep, BLV protects the total population of peripheral blood mononuclear cells (PBMCs) from ex vivo spontaneous apoptosis. This global decrease in the apoptosis rates resulted from both direct and indirect mechanisms which allow extension of cell survival. Although sheep are not natural hosts for BLV, these animals are prone to develop virus-induced leukemia at very high frequencies. Most infected cattle, however, remain clinically healthy. This difference in the susceptibilities to development of leukemia in these two species might be related to alterations of the apoptotic processes. Therefore, we designed this study to unravel the mechanisms of programmed cell death in cattle. We have observed that PBMCs from persistently lymphocytotic BLV-infected cows were more susceptible to spontaneous ex vivo apoptosis than cells from uninfected or aleukemic animals. These higher apoptosis rates were the consequence of an increased proportion of B cells exhibiting lower survival abilities. About one-third of the BLV-expressing cells did not survive the ex vivo culture conditions, demonstrating that viral expression is not strictly associated with cell survival in cattle. Surprisingly, culture supernatants from persistently lymphocytotic cows exhibited efficient antiapoptotic properties on both uninfected bovine and uninfected ovine cells. It thus appears that indirect inhibition of cell death can occur even in the presence of high apoptosis rates. Together, these results demonstrate that the protection against spontaneous apoptosis associated with BLV is different in cattle and in sheep. The higher levels of ex vivo apoptosis occurring in cattle might indicate a decreased susceptibility to development of leukemia in vivo.

scholarly journals Utilization of Pharmacological Ascorbate to Enhance Hydrogen Peroxide-Mediated Radiosensitivity in Cancer Therapy

2021 ◽  
Vol 22 (19) ◽  
pp. 10880
Author(s):  
Zain Mehdi ◽  
Michael S. Petronek ◽  
Jeffrey M. Stolwijk ◽  
Kranti A. Mapuskar ◽  
Amanda L. Kalen ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Dna Damage ◽  
Clinical Trials ◽  
Cell Death ◽  
Cancer Therapy ◽  
Normal Tissue ◽  
Normal Tissues ◽  
Cancer Cell Death ◽  
Radiation Induced ◽  
Early Phase Clinical Trials

Interest in the use of pharmacological ascorbate as a treatment for cancer has increased considerably since it was introduced by Cameron and Pauling in the 1970s. Recently, pharmacological ascorbate has been used in preclinical and early-phase clinical trials as a selective radiation sensitizer in cancer. The results of these studies are promising. This review summarizes data on pharmacological ascorbate (1) as a safe and efficacious adjuvant to cancer therapy; (2) as a selective radiosensitizer of cancer via a mechanism involving hydrogen peroxide; and (3) as a radioprotector in normal tissues. Additionally, we present new data demonstrating the ability of pharmacological ascorbate to enhance radiation-induced DNA damage in glioblastoma cells, facilitating cancer cell death. We propose that pharmacological ascorbate may be a general radiosensitizer in cancer therapy and simultaneously a radioprotector of normal tissue.

scholarly journals Lattice radiation therapy – its concept and impact in the immunomodulation cancer treatment era

2020 ◽  
Vol 66 (6) ◽  
pp. 728-731
Author(s):  
Antonio Cassio Assis Pellizzon
Keyword(s):  
Radiation Oncology ◽  
Dose Ratio ◽  
Low Dose Radiation ◽  
Normal Tissues ◽  
Dosimetric Characteristic ◽  
Radiation Induced ◽  
High Doses ◽  
Higher Doses ◽  
Dose Radiation

SUMMARY Voluminous tumors represent a challenge in radiation oncology, particularly when surgical resection is not possible. Lattice radiotherapy (LTR) is a technique that may provide equivalent or superior clinical response in the management of large tumors while limiting toxicity to adjacent normal tissues. LRT can precisely deliver inhomogeneous high doses of radiation to different areas within the gross tumor volumes (GTV). The dosimetric characteristic of LTR is defined by the ratio of the valley dose (lower doses – cold spots) and the peak doses, also called vertex (higher doses - hot spots), or the valley-to-peak dose ratio. The valley-to-peak ratio thereby quantifies the degree of spatial fractionation. LRT delivers high doses of radiation without exceeding the tolerance of adjacent critical structures. Radiobiological experiments support the role of radiation-induced bystander effects, vascular alterations, and immunologic interactions in areas subject to low dose radiation. The technological advancements continue to expand in Radiation Oncology, bringing new safety opportunities of treatment for bulky lesions.

scholarly journals Cellular FLICE-like inhibitory protein (cFLIP) critically maintains apoptotic resistance in human lens epithelial cells

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Jingru Huangfu ◽  
Caili Hao ◽  
Zongbo Wei ◽  
I. Michael Wormstone ◽  
Hong Yan ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cell ◽  
Cell Survival ◽  
Hela Cells ◽  
Ex Vivo ◽  
Cell Types ◽  
Lens Epithelial Cell ◽  
Human Lens ◽  
Inhibitory Protein ◽  
Almost All

AbstractThe present study aims to understand the mechanism of the lens epithelial cell’s strong anti-apoptotic capacity and survival in the mature human lens that, on the one hand, maintains lens transparency over several decades, while on the other hand, increases the risk of posterior capsule opacification (PCO). Here we compared FHL124 cells and HeLa cells, spontaneously immortalized epithelial cell lines derived from the human lens and cervical cancer cells, respectively, of their resistance to TNFα-mediated cell death. TNFα plus cycloheximide (CHX) triggered almost all of HeLa cell death. FHL124 cells, however, were unaffected and able to block caspase-8 activation as well as prevent caspase-3 and PARP-1 cleavage. Interestingly, despite spontaneous NFκB and AP-1 activation and upregulation of multiple cell survival/anti-apoptotic genes in both cell types, only FHL124 cells were able to survive the TNFα challenge. After screening and comparing the cell survival genes, cFLIP was found to be highly expressed in FHL124 cells and substantially upregulated by TNFα stimulation. FHL124 cells with a mild cFLIP knockdown manifested a profound apoptotic response to TNFα stimulus similar to HeLa cells. Most importantly, we confirmed these findings in an ex vivo lens capsular bag culture system. In conclusion, our results show that cFLIP is a critical gene that is regulating lens epithelial cell survival.

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