scholarly journals High LET Radiation Overcomes In Vitro Resistance to X-Rays of Chondrosarcoma Cell Lines

2019 ◽  
Vol 18 ◽  
pp. 153303381987130
Author(s):  
Francois Chevalier ◽  
Dounia Houria Hamdi ◽  
Charlotte Lepleux ◽  
Mihaela Temelie ◽  
Anaïs Nicol ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Lines ◽  
Relative Biological Effectiveness ◽  
Radiation Treatment ◽  
Malignant Tumors ◽  
Treatment Options ◽  
X Rays ◽  
Chondrosarcoma Cell ◽  
Biological Effectiveness

Chondrosarcomas are malignant tumors of the cartilage that are chemoresistant and radioresistant to X-rays. This restricts the treatment options essential to surgery. In this study, we investigated the sensitivity of chondrosarcoma to X-rays and C-ions in vitro. The sensitivity of 4 chondrosarcoma cell lines (SW1353, CH2879, OUMS27, and L835) was determined by clonogenic survival assays and cell cycle progression. In addition, biomarkers of DNA damage responses were analyzed in the SW1353 cell line. Chondrosarcoma cells showed a heterogeneous sensitivity toward irradiation. Chondrosarcoma cell lines were more sensitive to C-ions exposure compared to X-rays. Using D10 values, the relative biological effectiveness of C-ions was higher (relative biological effectiveness = 5.5) with cells resistant to X-rays (CH2879) and lower (relative biological effectiveness = 3.7) with sensitive cells (L835). C-ions induced more G2 phase blockage and micronuclei in SW1353 cells as compared to X-rays with the same doses. Persistent unrepaired DNA damage was also higher following C-ions irradiation. These results indicate that chondrosarcoma cell lines displayed a heterogeneous response to conventional radiation treatment; however, treatment with C-ions irradiation was more efficient in killing chondrosarcoma cells, compared to X-rays.

scholarly journals Investigating the impact of alpha/beta and LET d on relative biological effectiveness in scanned proton beams: An in vitro study based on human cell lines

2020 ◽  
Vol 47 (8) ◽  
pp. 3691-3702 ◽  
Author(s):  
Elisabeth Mara ◽  
Monika Clausen ◽  
Suphalak Khachonkham ◽  
Simon Deycmar ◽  
Clara Pessy ◽  
...  
Keyword(s):  
Cell Lines ◽  
Human Cell ◽  
Relative Biological Effectiveness ◽  
In Vitro Study ◽  
Vitro Study ◽  
Human Cell Lines ◽  
Biological Effectiveness ◽  
Alpha Beta ◽  
The Impact

scholarly journals Multiparametric radiobiological assays show that variation of X-ray energy strongly impacts relative biological effectiveness: comparison between 220 kV and 4 MV

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Vincent Paget ◽  
Mariam Ben Kacem ◽  
Morgane Dos Santos ◽  
Mohamed A. Benadjaoud ◽  
Frédéric Soysouvanh ◽  
...  
Keyword(s):  
Relative Biological Effectiveness ◽  
Clonogenic Assay ◽  
Umbilical Vein ◽  
High Energy ◽  
X Rays ◽  
X Ray ◽  
Biological Effectiveness ◽  
Umbilical Vein Endothelial Cells ◽  
Interventional Medicine

Abstract Based on classic clonogenic assay, it is accepted by the scientific community that, whatever the energy, the relative biological effectiveness of X-rays is equal to 1. However, although X-ray beams are widely used in diagnosis, interventional medicine and radiotherapy, comparisons of their energies are scarce. We therefore assessed in vitro the effects of low- and high-energy X-rays using Human umbilical vein endothelial cells (HUVECs) by performing clonogenic assay, measuring viability/mortality, counting γ-H2AX foci, studying cell proliferation and cellular senescence by flow cytometry and by performing gene analysis on custom arrays. Taken together, excepted for γ-H2AX foci counts, these experiments systematically show more adverse effects of high energy X-rays, while the relative biological effectiveness of photons is around 1, whatever the quality of the X-ray beam. These results strongly suggest that multiparametric analysis should be considered in support of clonogenic assay.

scholarly journals Thermal Neutron Relative Biological Effectiveness Factors for Boron Neutron Capture Therapy from In Vitro Irradiations

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2144
Author(s):  
María Pedrosa-Rivera ◽  
Javier Praena ◽  
Ignacio Porras ◽  
Manuel P. Sabariego ◽  
Ulli Köster ◽  
...  
Keyword(s):  
Thermal Neutron ◽  
Cell Lines ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Relative Biological Effectiveness ◽  
Neutron Capture Therapy ◽  
Boron Neutron Capture ◽  
Effectiveness Factors ◽  
Biological Effectiveness

The experimental determination of the relative biological effectiveness of thermal neutron factors is fundamental in Boron Neutron Capture Therapy. The present values have been obtained while using mixed beams that consist of both neutrons and photons of various energies. A common weighting factor has been used for both thermal and fast neutron doses, although such an approach has been questioned. At the nuclear reactor of the Institut Laue-Langevin a pure low-energy neutron beam has been used to determine thermal neutron relative biological effectiveness factors. Different cancer cell lines, which correspond to glioblastoma, melanoma, and head and neck squamous cell carcinoma, and non-tumor cell lines (lung fibroblast and embryonic kidney), have been irradiated while using an experimental arrangement designed to minimize neutron-induced secondary gamma radiation. Additionally, the cells were irradiated with photons at a medical linear accelerator, providing reference data for comparison with that from neutron irradiation. The survival and proliferation were studied after irradiation, yielding the Relative Biological Effectiveness that corresponds to the damage of thermal neutrons for the different tissue types.

scholarly journals Characterization of relative biological effectiveness for conventional radiation therapy: a comparison of clinical 6 MV X-rays and 137Cs

2017 ◽  
Vol 58 (5) ◽  
pp. 608-613 ◽  
Author(s):  
Michelle Howard ◽  
Chris Beltran ◽  
Jann Sarkaria ◽  
Michael G Herman
Keyword(s):  
Radiation Therapy ◽  
Cell Lines ◽  
Relative Biological Effectiveness ◽  
Chinese Hamster ◽  
High Energy ◽  
X Rays ◽  
Human Glioma ◽  
Biological Damage ◽  
Biological Effectiveness ◽  
Lung Adenocarcinoma A549

ABSTRACT Various types of radiation are utilized in the treatment of cancer. Equal physical doses of different radiation types do not always result in the same amount of biological damage. In order to account for these differences, a scaling factor known as the relative biological effectiveness (RBE) can be used. 137Cesium (137Cs) has been used as a source of radiation in a significant body of radiation therapy research. However, high-energy X-rays, such as 6 MV X-rays, are currently used clinically to treat patients. To date, there is a gap in the literature regarding the RBE comparison of these two types of radiation. Therefore, the purpose of this study was to investigate the RBE of 137Cs relative to that of 6 MV X-rays. To determine the RBE, five cell lines were irradiated [Chinese hamster ovary (CHO); human lung adenocarcinoma (A549); human glioma (U251); human glioma (T98); and human osteosarcoma (U2OS)] by both types of radiation and assessed for cell survival using a clonogenic assay. Three of the five cell lines resulted in RBE values of ~1.00 to within 11% for all survival fractions, showing the physical and biological dose for these two types of radiation were equivalent. The other two cell lines gave RBE values differing from 1.00 by up to 36%. In conclusion, the results show the range in biological effect seen between cell lines, and therefore cell type must be considered when characterizing RBE.

Bestimmung der DNA-Schädigung in vitro

2010 ◽  
Vol 49 (S 01) ◽  
pp. S64-S68
Author(s):  
E. Dikomey
Keyword(s):  
Dna Damage ◽  
Cell Lines ◽  
Chromosome Aberrations ◽  
Genetic Factors ◽  
Double Strand Breaks ◽  
Strand Breaks ◽  
Cell Inactivation ◽  
Repair Mechanisms ◽  
Break Repair

SummaryIonising irradiation acts primarily via induction of DNA damage, among which doublestrand breaks are the most important lesions. These lesions may lead to lethal chromosome aberrations, which are the main reason for cell inactivation. Double-strand breaks can be repaired by several different mechanisms. The regulation of these mechanisms appears be fairly different for normal and tumour cells. Among different cell lines capacity of doublestrand break repair varies by only few percents and is known to be determined mostly by genetic factors. Knowledge about doublestrand break repair mechanisms and their regulation is important for the optimal application of ionising irradiation in medicine.

Stew in its Own Juice: Protein Homeostasis Machinery Inhibition Reduces Cell Viability in Multiple Myeloma Cell Lines

2019 ◽  
Vol 19 (2) ◽  
pp. 112-119 ◽  
Author(s):  
Mariana B. de Oliveira ◽  
Luiz F.G. Sanson ◽  
Angela I.P. Eugenio ◽  
Rebecca S.S. Barbosa-Dantas ◽  
Gisele W.B. Colleoni
Keyword(s):  
Multiple Myeloma ◽  
Cell Death ◽  
Cell Viability ◽  
Cell Lines ◽  
Treatment Options ◽  
Compensatory Mechanism ◽  
Protein Homeostasis ◽  
Protein Response ◽  
Rpmi 8226

Introduction:Multiple myeloma (MM) cells accumulate in the bone marrow and produce enormous quantities of immunoglobulins, causing endoplasmatic reticulum stress and activation of protein handling machinery, such as heat shock protein response, autophagy and unfolded protein response (UPR).Methods:We evaluated cell lines viability after treatment with bortezomib (B) in combination with HSP70 (VER-15508) and autophagy (SBI-0206965) or UPR (STF- 083010) inhibitors.Results:For RPMI-8226, after 72 hours of treatment with B+VER+STF or B+VER+SBI, we observed 15% of viable cells, but treatment with B alone was better (90% of cell death). For U266, treatment with B+VER+STF or with B+VER+SBI for 72 hours resulted in 20% of cell viability and both treatments were better than treatment with B alone (40% of cell death). After both triplet combinations, RPMI-8226 and U266 presented the overexpression of XBP-1 UPR protein, suggesting that it is acting as a compensatory mechanism, in an attempt of the cell to handle the otherwise lethal large amount of immunoglobulin overload.Conclusion:Our in vitro results provide additional evidence that combinations of protein homeostasis inhibitors might be explored as treatment options for MM.

scholarly journals Lomeguatrib Increases the Radiosensitivity of MGMT Unmethylated Human Glioblastoma Multiforme Cell Lines

2021 ◽  
Vol 22 (13) ◽  
pp. 6781
Author(s):  
Anna Kirstein ◽  
Daniela Schilling ◽  
Stephanie E. Combs ◽  
Thomas E. Schmid
Keyword(s):  
Glioblastoma Multiforme ◽  
Cell Lines ◽  
Dna Methyltransferase ◽  
Treatment Options ◽  
Treatment Resistance ◽  
Cell Cycle Distribution ◽  
Human Glioblastoma ◽  
Human Glioblastoma Multiforme ◽  
Mgmt Protein

Background: Treatment resistance of glioblastoma multiforme to chemo- and radiotherapy remains a challenge yet to overcome. In particular, the O6-methylguanine-DNA-methyltransferase (MGMT) promoter unmethylated patients have only little benefit from chemotherapy treatment using temozolomide since MGMT counteracts its therapeutic efficacy. Therefore, new treatment options in radiotherapy need to be developed to inhibit MGMT and increase radiotherapy response. Methods: Lomeguatrib, a highly specific MGMT inhibitor, was used to inactivate MGMT protein in vitro. Radiosensitivity of established human glioblastoma multiforme cell lines in combination with lomeguatrib was investigated using the clonogenic survival assay. Inhibition of MGMT was analyzed using Western Blot. Cell cycle distribution and apoptosis were investigated to determine the effects of lomeguatrib alone as well as in combination with ionizing radiation. Results: Lomeguatrib significantly decreased MGMT protein and reduced radiation-induced G2/M arrest. A radiosensitizing effect of lomeguatrib was observed when administered at 1 µM and increased radioresistance at 20 µM. Conclusion: Low concentrations of lomeguatrib elicit radiosensitization, while high concentrations mediate a radioprotective effect.

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