This article discusses the different types of radiation therapy, including how they work and the side effects and risks. It also explains what a person can expect from radiation therapy and the likely outcome.
Radiation Photoshop Action
DOWNLOAD: https://shoxet.com/2vFkxC
Some people might receive radiation therapy before surgery to shrink a tumor and make it easier to remove. Other individuals might receive it after surgery to destroy cancer cells that the surgery may have missed.
It is important to note that a person cannot receive an unlimited amount of radiation. Therefore, doctors restrict the therapy to one part of the body and limit the total amount that a person receives over their lifetime.
Quantitative analysis of nerve damage induced by ultraviolet (UV) radiation and assessment of neuroprotection. Skin samples left untreated, treated with emulsions only (Cream 1, Cream 2 or SPF 15), exposed to UVA or UVB, or pretreated with emulsions (Cream 1, Cream 2 or SPF 15) then exposed to UVA or UVB ex vivo. Statistically significant differences indicated: **P
Effects of ultraviolet (UV) radiation on skin samples obtained from breast (n = 15) or abdomen (n = 19) tissues. Skin samples left untreated, treated with emulsions only (Cream 1, Cream 2), exposed to UVA or UVB, or pretreated with emulsions (Cream 1, Cream 2) then exposed to UVA or UVB ex vivo. Statistically significant differences indicated: **P
A landmark three part 2021 research review on effects to wildlife published in Reviews on Environmental Health by U.S experts including former U.S. Fish and Wildlife senior biologist Albert Manville states current science should trigger urgent regulatory action citing more than 1,200 scientific references which found adverse biological effects to wildlife from even very low intensities of non ionizing radiation with findings of impacts to orientation and migration, reproduction, mating, nest, den building and survivorship (Levitt et al., 2021a, Levitt et al., 2021b, Levitt et al., 2021c).
U118 gliobastoma cell lines were treated under various standard of care combinations (untreated, radiation and chemotherapeutic) prior to infection with MYXV. Infection was then monitored for differences in rate of infection, titer and rate of spread. Cellular death was measured by MTT assay and Caspase-3 colorimetric assay. Patient biopsies were harvested and treated under similar treatment conditions.
The addition of GBM standard of care to MYXV infection resulted in an increased rate of spread compared to single treatment with either radiation or chemotherapeutic alone. SOC did not alter viral replication or infection rates. Similar effects were seen in ex vivo patient biopsies. Cellular viability was significantly decreased with the combination therapy of SOC and MYXV infection compared to any other treatment outcome. Caspase-3 activity was also significantly increased in samples treated with combination therapy when compared to any other treatment combination.
We next set out to determine if the combination of viral treatment and SOC would increase killing of GBM. In order to assess this, we assayed cellular viability and Caspase-3 activity following treatment with MXYV in either the presence or absence of SOC. U118, T9 and GL261 cells were infected at an MOI of 15 in either the presence or absence of radiation, chemotherapeutic agent, or SOC. Measurements were taken at 72 hours post treatment. While all mono-therapies decreased cellular viability to some extent, we observed that the combination therapy, including MYXV, radiation and a chemotherapeutic drug resulted in significantly higher decrease in cell viability compared to any other condition (Figure 3A). These results were consistent across all three chemotherapeutic drugs tested. Similarly, when using either Bevacizumab or Crizotinib as the chemotherapeutic drug, we observed a significant increase in Caspase-3 activity when cells were treated with the triple combination of MYXV, radiation, and drug (Figure 3B). Interestingly, we observed a much lower increase in Caspase-3 activity with Temozolomide with either of the two other chemotherapeutic agents, though it was still significantly different from that with SOC combined with radiation and MYXV (Figure 3B). Consistent with these results, we observed both increased levels of cleaved Caspase-3 and decreased phosphorylation of AKT in samples treated with MYXV and SOC (Figure 3C). To again confirm the previous results in primary GBM samples, experiments similar to those described above were performed in primary GBM patient biopsies. Similar to what was seen in cell lines, the results demonstrated that the combination of MYXV and SOC significantly reduced cellular viability of primary GBM cells, more than other treatment regimens (Figure 4A). This reduction in cellular viability was again correlated with increased Caspase-3 activity and cleavage as well as decreased phosphorylation of AKT (Figure 4B and C). Oncolytic myxoma virus synergizes with standard of care for treatment of glioblastoma multiformeAll authorsChase Burton, Arabinda Das, Daniel McDonald, William A Vandergrift III, Sunil J Patel, David Cachia & Eric Bartee online:21 December 2022Figure 3 In vitro analysis of cell viability of combined treatment conditions.
The poor outcomes of a GBM diagnosis have remained static over the years. However, OV is to be considered a promising novel treatment option for GBM.Citation20 Current oncolytic viruses, including adenovirus, newcastle disease virus, herpes simplex virus, poliovirus, measles virus, H1 parvovirus, reovirus and vaccinia virus have been tested against GBM models and have shown therapeutic efficacy.Citation31,Citation32 While these viruses have shown oncolytic potential, there is risk associated with their natural human pathogenicity. In light of this, MYXV a nonhuman pathogenic virus which has previously been shown to be an effective oncolytic virus against multiple myeloma,Citation33 has shown efficacy as a potential GBM treatment.Citation34 While there is some literature which suggests that the combination of MYXV and chemotherapeutics, such as rapamyacin,Citation22 may increase the efficacy of treatment, little work has been done to elucidate the interaction between MYXV and SOC for GBM. In this study, we were able to show that MYXV is a suitable oncolytic virus for GBM in vitro and synergistically increases efficacy when combined with SOC.
In order to be effective, oncolytic viruses must initiate infection and successfully replicate within tumor cells, resulting in cell death. Our results indicate that combining MYXV with SOC does not alter initial infection or the ability of MYXV to replicate in GBM cells. Importantly, we did observe that viral spread was increased upon MYXV infection with both radiation and Temozolomide. Furthermore, a similar result was observed in patient biopsies in terms of fluorescence, both with and without radiation. Interestingly, we observe a discrepancy between the in vitro cell lines and ex vivo patient biopsies in terms of viral spread in the presence of radiation. We hypothesize that this discrepancy is due to the makeup of the patient biopsies compared to cells grown in culture. While cultured cells offer a fairly homozygous population, patient biopsies are comprised of a diverse cellular makeup. It is possible that the patient biopsies then react differently to radiation and viral treatment than how cultured cells do, resulting in the observed discrepancy of spread between samples. Additionally, differences between these two samples sets could be related to tumor treatment prior to the harvesting of the biopsy. It is possible that part of the initial treatment primed the cells in the biopsies to allow for increased spread, priming which cultured cells would not have undergone. The differences between initial infection and spread are curious, and merit further inquiry, particularly in terms of patient biopsies, as they are the most clinically relevant model. This could be due to a number of factors, including alterations in cellular morphology, such as cellular junctions, which allows MYXV to spread between the cells more effectively than under normal conditions. Additionally, treatment of the cells with SOC could result in the increased ability of the virus to egress from infected cells, either through changes in cellular permeability or by some other mechanism, and would explain the differences in the foci forming assay but not in the single step growth curve or the initial infection assay.
We next decided to check the effect that our treatment protocol had on cell viability by both, an MTT assay and Caspase-3 colorimetric assay. The results of our MTT assay show that the combination of SOC and MYXV greatly reduced cell viability compared to either treatment alone. This increase correlated with similar increases in Caspase-3 activation following SOC using all three chemotherapeutic drugs. Interestingly, while all drugs showed an increase in Caspase-3 activity when combined with MYXV, a markedly smaller increase was observed when using temozolomide compared to either Bevacizumab or Crizotinib. We hypothesize that this is the result of different mechanisms of action for each chemotherapeutic drug. Temozolomide methylates the DNA of cells, whereas Bevacizumab targets the VEGF/VEGF-R interaction to prevent cell survival. Another possibility is the half-life of Temozolomide, which is 1.8 hours in vitro. This could potentially hinder treatment outcomes, especially over the course of experiments which extend out several days. These differences could lead to cell death through pathways other than Caspase-3, and thus explain the differences we observed between p-Akt and Caspase-3 levels. Future studies are needed to find the true cause of this difference.
In addition to our work in cell lines, we also tested the combination of MYXV and SOC in primary GBM patient biopsies. We first saw that the addition of radiation to the patient samples resulted in increased GFP expression in tumor slices, even in the absence of chemotherapeutic drug. These results differ somewhat from our results with cultured cells where the addition of both radiation and drug was needed to increase viral spread. This could be due to the makeup of patient biopsies, as they contain more heterogeneous cell populations than purified cultured cell lines. SOC may therefore affect individual populations of cells differently and may explain the inconsistent results between the biopsies and cultured cells. Further investigation into in vivo models is needed in order to determine the potential cause of this difference and make the results more clinically relevant to patient care. 2ff7e9595c
Comments